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Background.Studies indicate that following septic insult there is development of generalized immune dysfunction in T cells, B cells and phagocytes, which is thought to contribute to morbidity and mortality. Specifically, there is a shift in the lymphocytes of septic animals toward an increased release of Th2 cytokines. NK-T cells have been shown to contribute to propagation of the Th2 response. The influence of NK-T cells on the immune response to septic challenge is poorly understood. In this study, we examine whether NK-T cells contribute to the immune dysfunction seen following the onset of polymicrobial sepsis, as produced by cecal ligation and puncture (CLP).Materials and methods.Male 129S1/SvImJ mice were pretreated with either rat IgG (isotypic control) or monoclonal antibody to CD1d (clone 1B1) (0.5 mg), which blocks signaling/antigen presentation via the CD1d cell surface receptor, thereby, ablating the activation and differentiation of the NK-T cells. Septic survival with and without anti-CD1d (CLP/CD1d) pretreatment was assessed. Mice sacrificed 24 h after CLP were assessed for change in splenic %NK-T cell (via flourescense activated cell sector) and for splenic, hepatic, and lymphoid/macrophage production of pro-inflammatory or anti-inflammatory cytokines (via enzyme-linked immunosorbent assay).Results.Administration of anti-CD1d reduced septic mortality 35% at 6–10 d (n = 23 mice/group) (P < .05). There was a consistent increase in the %CD3+ NK1.1+ cell population (NK-T cells) in septic mice (1.706%), which was markedly suppressed by pretreatment with anti-CD1d (0.592%). IL-6 and IL-10 levels were suppressed by anti-CD1d in the spleen and blood.Conclusions.Together these findings imply not only that NK-T cells may play a role in mediating the immune suppression seen in bacterial sepsis, but that inhibition of their activation promotes survival to septic challenge. [Copyright &y& Elsevier]

Spleen tyrosine kinase (Syk) is a non-receptor protein tyrosine kinase, and it mediates downstream signaling of FcR-mediated immune responses. Our previous work revealed that the expression of Syk was significantly up-regulated in flounder mIgM+ B lymphocytes after phagocytosis of antiserum-opsonized Edwardsiella tarda , which suggested Syk might be involved in Ig-opsonized phagocytosis. In this paper, phospho-Syk (pSyk) inhibitor was used to investigate the potential role of phosphorylated Syk in FcR-mediated phagocytosis of IgM+ B cells. Indirect immunofluorescence assay (IFA) and Western blotting showed that the level of phosphorylated Syk in the mIgM+ B lymphocytes treated with pSyk inhibitor was significantly lower compared to the control group after stimulation with flounder antiserum. Flow cytometry analysis showed that after 3 h incubation with antiserum-opsonized E. tarda , the phagocytosis rates of mIgM+ B lymphocytes from peripheral blood, spleen and head kidney pre-treated with pSyk inhibitor were 48.1%, 40.1% and 43.6% respectively, which were significantly lower than that of the control groups with 58.7%, 53.2% and 57.4%, respectively. And likewise, after pSyk inhibitor treatment, the proportions of mIgM+ B lymphocytes with higher intracellular reactive oxygen species (ROS) levels in peripheral blood, spleen and head kidney decreased to 15.2%, 12.0% and 12.1% from the control level of 26.5%, 25.9% and 26.3%, respectively. Moreover, the expression of three genes affected by pSyk, including phospholipase Cγ1 (PLCγ1), phospholipase Cγ2 (PLCγ2) and phosphatidylinositol 3 kinase (PI3K) were found to be significantly down-regulated in pSyk inhibitor-treated mIgM+ B lymphocytes post phagocytosis. These results suggest that pSyk plays a key role in FcR-mediated phagocytosis and bactericidal activity of mIgM+ B lymphocytes, which promotes further understanding of the regulatory role of pSyk in teleost B cells phagocytosis. • The first study to find that the activated FcR could induce phosphorylation of Syk in flounder mIgM + B lymphocytes. • The pSyk played a key role in FcR-mediated phagocytosis and bactericidal activity of flounder mIgM+ B lymphocytes. • The pSyk was essential for ADCP-related downstream signaling in flounder mIgM+ B lymphocytes. [ABSTRACT FROM AUTHOR]

For a simply connected connected simple algebraic group G , a cell B w 0 − = B − ∩ U w 0 ‾ U is a geometric crystal with a positive structure θ i − : (C ×) l (w 0) → B w 0 −. Applying the tropicalization functor to a rational function Φ B K h = ∑ i ∈ I Δ w 0 Λ i , s i Λ i called the half decoration on B w 0 − , one can realize the crystal B (∞) in Z l (w 0). By computing Φ B K h , we get an explicit form of B (∞) in Z l (w 0). In this paper, we give an algorithm to compute Δ w 0 Λ i , s i Λ i ∘ θ i − explicitly for i ∈ I such that V (Λ i) is a minuscule representation of g = Lie (G). In particular, the algorithm works for all i ∈ I if g is of type A n. The algorithm computes a directed graph DG , called a decoration graph , whose vertices are labelled by all monomials in Δ w 0 Λ i , s i Λ i ∘ θ i − (t 1 , ⋯ , t l (w 0)). The decoration graph has some properties similar to crystal graphs of minuscule representations. We also verify that the algorithm works in some other cases, for example, the case g is of type G 2 though V (Λ i) is non-minuscule. [ABSTRACT FROM AUTHOR]

The phagocytic actives of B cells in fish have been proven in recent years. In this study, five positive hybridomas secreting monoclonal antibodies (MAbs) against largemouth bass IgM were produced. Indirect immunofluorescence assay (IFA) demonstrated that five MAbs could specifically recognize membrane-bound IgM (mIgM) molecule of largemouth bass. Indirect ELISA and Western blotting analysis showed that all the five MAbs had no cross-reactions with the other two teleost IgMs. Flow cytometry analysis (FCM) revealed that the percentages of largemouth bass mIgM+ lymphocytes in head kidney, peripheral blood and spleen were 51.66 ± 0.608%, 16.5 ± 1.235% and 42.92 ± 1.091%, respectively. In addition, the phagocytosis rates of mIgM + lymphocytes ingesting Nocardia seriolae from head kidney, peripheral blood and spleen were calculated to be 5.413 ± 0.274%, 16.6 ± 0.289% and 26.3 ± 0.296%, respectively. The qPCR results of sorted cells indicated that most inflammatory cytokines (IFNγ, IL-1β, IL-2, IL-12β, IL-34, IL-10) , chemokine (CXCL12), chemokines receptors (CXCR2, CXCR4) and genes (FcγRⅠa, NCF1, CFL, ARP2/3, CD45, Syk, MARCKS) related to FcγR-mediated phagocytic signaling pathway in phagocytic mIgM+ lymphocytes were up-regulated significantly (P < 0.05). Taken together, the results suggested that the MAb (MM06H) produced in this paper could be used as a tool to study mIgM+ lymphocytes of largemouth bass, and FcγR may participate in the phagocytosis of mIgM+ lymphocytes, which is helpful to further study the role of mIgM+ lymphocytes in innate immunity. • Monoclonal antibodies against Micropterus salmoides were produced. • The phagocytosis of mIgM+ lymphocytes from largemouth bass was validated. • 33 immune-related genes of sorted phagocytic mIgM+ lymphocytes were up-regulated. • FcγR-mediated phagocytosis pathway may participate in the phagocytosis of mIgM+ lymphocytes. [ABSTRACT FROM AUTHOR]

Interleukin-2 receptor (IL-2R), as the specific ligand of interleukin-2 (IL-2), binds to IL-2 and transmits signals and then can induce the proliferation of T lymphocytes in mammals. In this paper, the subunit of IL-2R in flounder (Paralichthys olivaceus), interleukin-2 receptor subunit gamma (IL-2Rγ) was cloned, and polyclonal antibodies (Abs) against its extracellular region were produced, then the expression of flounder IL-2Rγ (fIL-2Rγ) at transcriptional and cellular levels were characterized. Moreover, the interaction of flounder IL-2 (fIL-2) with fIL-2Rγ was investigated, and the variations on CD4+/IL-2Rγ+ cells in flounder after treatment with recombinant IL-2 (rIL-2), anti-IL-2Rγ Abs were detected, respectively. The results showed that fIL-2Rγ protein had a typical fibronectin type III (FN3) domain. The Abs could specifically recognize native fIL-2Rγ molecules at 39.9 kDa. FIL-2Rγ was localized on both T and B lymphocytes, and the percentages of CD4+/IL-2Rγ+ and IgM+/IL-2Rγ+ lymphocytes were high in spleen. In addition, pBiFC-VN173-IL-2Rγ plasmids could bind to pBiFC-VC155-IL-2 plasmids. The percentage of CD4+/IL-2Rγ+ lymphocytes was significantly decreased after blocking with anti-IL-2Rγ Abs both in vivo and in vitro. In the meantime, four T cell markers genes and six IL-2-IL-2R pathway genes were down-regulated in anti-IL-2Rγ Abs group. These results first demonstrated that fIL-2Rγ molecules were expressed on both T and B lymphocytes in flounder, and the bond between fIL-2Rγ and fIL-2 activated the CD4 T lymphocytes. This study gave a new sight into the exploration of IL-2R function on T lymphocytes proliferation in fish. • IL-2Rγ mRNA was highly expressed in peripheral blood leukocytes, spleen and head kidney in flounder. • IL-2Rγ molecules were localized on both T and B lymphocytes in flounder. • Flounder IL-2 could bind to flounder IL-2Rγ. • The addition of recombinant IL-2 significantly increased the percentage of CD4+/IL-2Rγ+ lymphocytes at 72 h. [ABSTRACT FROM AUTHOR]

Immunological memory can be regarded as the key aspect of adaptive immunity, i.e. a specific response to first contact with an antigen, which in mammals is determined by the properties of T, B and NK cells. Re-exposure to the same antigen results in a more rapid response of the activated specific cells, which have a unique property that is the immunological memory acquired upon first contact with the antigen. Such a state of immune activity is also to be understood as related to "altered behavior of the immune system" due to genetic alterations, presumably maintained independently of the antigen. It also indicates a possible alternative mechanism of maintaining the immune state at a low level of the immune response, "directed" by an antigen or dependent on an antigen, associated with repeated exposure to the same antigen from time to time, as well as the concept of innate immune memory, associated with epigenetic reprogramming of myeloid cells, i.e. macrophages and NK cells. Studies on Teleostei have provided evidence for the presence of immunological memory determined by T and B cells and a secondary response stronger than the primary response. Research has also demonstrated that in these animals macrophages and NK-like cells (similar to mammalian NK cells) are able to respond when re-exposed to the same antigen. Regardless of previous reports on immunological memory in teleost fish, many reactions and mechanisms related to this ability require further investigation. The very nature of immunological memory and the activity of cells involved in this process, in particular macrophages and NK-like cells, need to be explained. This paper presents problems associated with adaptive and innate immune memory in teleost fish and characteristics of cells associated with this ability. • The presence of adaptive and innate immune memory has been confirmed in fish. • Adaptive immune memory in fish develops with the participation of T and B lymphocytes. • Innate immune memory is related to the properties of macrophages and NK-like cells. • There is a need to further verify the biological basis of this property. [ABSTRACT FROM AUTHOR]

Let (W a , S a) be an irreducible affine Weyl group with W 0 the associated Weyl group. In my previous paper [24] , I proved that the number n qr of left cells of W a in the second lowest two-sided cell Ω qr satisfies the inequality n qr ⩽ 1 2 | W 0 | and conjectured that the equality should actually hold. In the present paper, we verify the conjecture when W a = B ˜ n ; we prove that any left cell of B ˜ n in Ω qr is left-connected, verifying a conjecture of Lusztig in our case; we show that Ω qr consists of all the extensions of w J in the set B ˜ n − W (ν) , where W (ν) is the lowest two-sided cell of B ˜ n and J ⊂ S a is such that w J is the longest element in the subgroup W J of B ˜ n of type D n. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a typical systemic autoimmune disease that manifests as skin rash, arthritis, lymphadenopathy, and multiple organ lesions. Epigenetics, including DNA methylation, histone modification, and non-coding RNA regulation, mainly affect the function and characteristics of cells through the regulation of gene transcription or translation. Increasing evidence indicates that there are a variety of complex epigenetic effects in patients with SLE, which interfere with the differentiation and function of T, and B lymphocytes, monocytes, and neutrophils, and enhance the expression of SLE-associated pathogenic genes. This paper summarizes our currently knowledge regarding pathogenesis of SLE, and introduces current advances in the epigenetic regulation of SLE from three aspects: immune function, inflammatory response, and lupus complications. We propose that epigenetic changes could be used as potential biomarkers and therapeutic targets of SLE. • Epigenetic modifications are widely involved in the pathogenesis of SLE. • Epigenetic modifications promote and maintain continuous immune activation and chronic inflammation. • Epigenetic modifications promote and maintain continuous immune activation and chronic inflammation. [ABSTRACT FROM AUTHOR]

This paper summarizes and reviews the mechanisms of action and data concerning efficacy of recommended treatments as well as other treatments that have been tested, independently of the outcomes, in the management of chronic spontaneous urticaria. Due to the central role of mast cells, basophils and histamine in the pathophysiology of this disease, H 1 -antihistamines remain the first-line treatment. However, current knowledge about this complex disease, also recognizes an important role for T lymphocytes, B lymphocytes, and autoantibodies. Implications of these others mediators thus provide further targets for treatment. Indeed, agents previously used to treat other autoimmune and inflammatory diseases, have demonstrated efficacy in chronic spontaneous urticaria and are therefore potential therapeutic alternatives for antihistamine unresponsive patients. [ABSTRACT FROM AUTHOR]

In this paper, we use RNAseq to identify senescence and phagocytosis as key factors to understanding how mitomyin C (MMC) stimulates regenerative wound repair. We use conditioned media (CM) from untreated (CMC) and MMC treated (CMM) human and mouse corneal epithelial cells to show that corneal epithelial cells indirectly exposed to MMC secrete elevated levels of immunomodulatory proteins including IL-1α and TGFβ1 compared to cells exposed to CMC. These factors increase epithelial and macrophage phagocytosis and promote ECM turnover. IL-1α supplementation can increase phagocytosis in control epithelial cells and attenuate TGFβ1 induced αSMA expression by corneal fibroblasts. Yet, we show that epithelial cell CM contains factors besides IL-1α that regulate phagocytosis and αSMA expression by fibroblasts. Exposure to CMM also impacts the activation of bone marrow derived dendritic cells and their ability to present antigen. These in vitro studies show how a brief exposure to MMC induces corneal epithelial cells to release proteins and other factors that function in a paracrine way to enhance debris removal and enlist resident epithelial and immune cells as well as stromal fibroblasts to support regenerative and not fibrotic wound healing. • RNAseq shows increased expression of phagocytosis related genes in response to transient MMC treatment of corneal epithelial cells. • Growing corneal epithelial cells and macrophages in conditioned media secreted by MMC-treated corneal epithelial cells activates phagocytosis. • Conditioned media from MMC treated human corneal epithelial cells contains more IL-1α and TGFβ1. • Conditioned media from MMC treated human corneal epithelial cells increases dendritic cell activation but suppresses T cell differentiation in antigen presentation assays. [ABSTRACT FROM AUTHOR]

In acquired immunity, T lymphocytes regulate the immune responses of B lymphocytes, including the IgM + B lymphocyte counts and antibody production. In this paper, Cyclosporine A (CsA) and Rapamycin (RaPa) were used, and their inhibition on T lymphocytes and immune responses of B lymphocytes in flounder ( Paralichthys olivaceus ) were investigated. Flounder was injected with Keyhole Limpet Hemocyanin (KLH), a mixture of KLH and CsA (KLH + CsA), or a mixture of KLH and RaPa (KLH + RaPa). Then, the proportions of T and IgM + B lymphocytes (PT and PB) in peripheral blood leukocytes (PBL) were analysed by flow cytometry (FCM), total antibodies (TA) and KLH specific antibodies (KA) in serum were measured by ELISA, and expression of 9 immune-related genes in the spleen and kidneys were determined using q-PCR. On the other hand, the PBL culture was treated with Concanavalin A (ConA), a mixture of ConA and CsA, and a mixture of ConA and RaPa. Then the PT and PB were measured, and the cell proliferation was examined using the MTT method. The results showed that the PT peaked on the 5 th day in the KLH group, KLH + CsA group and KLH + RaPa group. The maximum inhibition rates (MIR) of CsA and RaPa were 27.44% ± 0.50% and 21.37% ± 2.06%, respectively. The PB peaked at the 5 th week, and the MIR of CsA and RaPa were 44.51% ± 1.36% and 33.3% ± 0.65%, respectively. The KA and TA peaked at the 5 th week. The MIR of CsA and RaPa on TA were 40.31% ± 1.59% and 32.96% ± 2.21%, respectively, and were 27.77% ± 2.02% and 23.41% ± 1.08% for KA, respectively. Nine immune-related genes had significantly lower expression in the KLH + CsA group and KLH + RaPa group compared to the KLH group. The proliferation of the PBL culture was inhibited by CsA or RaPa, and the inhibition rate of CsA and RaPa for PT was 18.14% ± 1.08% and 17.88% ± 1.02%, respectively, and the inhibition rates for PB were 3.03% ± 0.57% and 2.95% ± 0.53%, respectively. The results demonstrated that T lymphocytes counts were inhibited by CsA and RaPa, followed by suppression of IgM + B lymphocytes and antibody production, which suggests that T lymphocytes regulate the immune response of B lymphocytes in flounder. [ABSTRACT FROM AUTHOR]

Monocytic myeloid-derived suppressor cells (M-MDSCs) were increased during LP-BM5 retroviral infection, and were capable of suppressing not only T-cell, but also B-cell responses. In addition to previously demonstrating iNOS- and VISTA-dependent M-MDSC mechanisms, in this paper, we detail how M-MDSCs utilized soluble mediators, including the reactive oxygen and nitrogen species superoxide, peroxynitrite, and nitric oxide, and TGF-β, to suppress B cells in a predominantly contact-independent manner. Suppression was independent of cysteine-depletion and hydrogen peroxide production. When two major mechanisms of suppression (iNOS and VISTA) were eliminated in double knockout mice, M-MDSCs from LP-BM5-infected mice were able to compensate using other, soluble mechanisms in order to maintain suppression of B cells. The IL-10 producing regulatory B-cell compartment was among the targets of M-MDSC-mediated suppression. [ABSTRACT FROM AUTHOR]

Abstract: One of the first immunologic responses against HIV infection is the presence of neutralizing antibodies that seem able to inactivate several HIV strains. Moreover, in vitro studies have shown the existence of monoclonal antibodies that exhibit broad crossclade neutralizing potential. Yet their number is low and slow to develop in vivo. In this paper, we investigate the potential benefits of inducing poly-specific neutralizing antibodies in vivo throughout immunization. We develop a mathematical model that considers the activation of families of B lymphocytes producing poly-specific and strain-specific antibodies and use it to demonstrate that, even if such families are successful in producing neutralizing antibodies, the competition between them may limit the poly-specific response allowing the virus to escape. We modify this model to account for viral evolution under the pressure of antibody responses in natural HIV infection. The model can reproduce viral escape under certain conditions of B lymphocyte competition. Using these models we provide explanations for the observed antibody failure in controlling natural infection and predict quantitative measures that need to be satisfied for long-term control of HIV infection. [Copyright &y& Elsevier]

Abstract: Control of lymphocyte homeostasis is essential to ensure efficient immune responses and to prevent autoimmunity. Splenic marginal zone B cells are important producers of autoantibodies, and are subject to stringent tolerance mechanisms to prevent autoimmunity. In this paper, we explore the role of the Mer tyrosine kinase (Mertk) in regulating autoreactive B cells. This receptor tyrosine kinase serves to bind apoptotic cells, to mediate their phagocytosis, and to regulate subsequent cytokine production. Mice lacking Mertk suffer from impaired apoptotic cell clearance and develop a lupus-like autoimmune syndrome. Here we show that such Mertk-KO mice have expanded numbers of splenic marginal zone B cells. Mertk-KO mice bearing a DNA-specific immunoglobulin heavy-chain transgene (3H9) produced anti-DNA antibodies that appeared to be secreted largely by marginal zone B cells. Finally, Mertk-KO mice developed greater antibody responses after NP-Ficoll immunization than their B6 counterparts. Taken together, our data show that Mertk has a major effect on the development of the marginal zone B-cell compartment. Mertk is also important in establishing DNA-specific B-cell tolerance in 3H9 anti-DNA transgenic mice. [Copyright &y& Elsevier]

Abstract: DNA transfection can be too inefficient to establish a desired number of stable transfectants, particularly in lymphocytes; however, this could be circumvented by increasing the absolute frequency of random integration. In this paper, we show that treating cells with topoisomerase II inhibitor following electroporation greatly (∼10- to 20-fold) enhances random integration of input DNA in a human pre-B lymphocyte cell line, Nalm-6. With the use of various kinds of topoisomerase II-targeting agents, we also present evidence that topoisomerase IIα inhibition is critical for the enhancement of random integration, while the contribution of topoisomerase IIβ may be negligible. As topoisomerase IIα is highly expressed in vigorously growing cells, our results show that topoisomerase IIα inhibition provides a promising way of enhancing random integration in virtually all cultured cell lines. [Copyright &y& Elsevier]

• B lymphopoiesis is a regulated process that leads to the formation of B cells. • We describe a compartmental mathematical model of feedback signalling for B cells. • We provide a mathematical analysis of homeostasis and compare with clinical data. • Regulation of proliferation is key to the maintenance of a steady state. • We also analyse parameter influence in simulations of immune reconstitution. Haematopoiesis is the process of generation of blood cells. Lymphopoiesis generates lymphocytes, the cells in charge of the adaptive immune response. Disruptions of this process are associated with diseases like leukaemia, which is especially incident in children. The characteristics of self-regulation of this process make them suitable for a mathematical study. In this paper we develop mathematical models of lymphopoiesis using currently available data. We do this by drawing inspiration from existing structured models of cell lineage development and integrating them with paediatric bone marrow data, with special focus on regulatory mechanisms. A formal analysis of the models is carried out, giving steady states and their stability conditions. We use this analysis to obtain biologically relevant regions of the parameter space and to understand the dynamical behaviour of B-cell renovation. Finally, we use numerical simulations to obtain further insight into the influence of proliferation and maturation rates on the reconstitution of the cells in the B line. We conclude that a model including feedback regulation of cell proliferation represents a biologically plausible depiction for B-cell reconstitution in bone marrow. Research into haematological disorders could benefit from a precise dynamical description of B lymphopoiesis. [ABSTRACT FROM AUTHOR]

This paper evaluates the expression and functional significance of PPAR-γ on human B cells. Recent interest in PPAR-γ has focused on its adipogenic effects on non-bone marrow-derived cells. PPAR-γ agonists also have been proposed as anti-inflammatory agents owing to inhibition of NF-κB activation. We report herein the first study evaluating PPAR-γ expression and functional significance in human B lineage cells. Interestingly, normal human B cells and a variety of B lymphoma cells (e.g., Daudi, Ramos, and Raji) express PPAR-γ protein as determined by immunocytochemistry. The expression of 80-kDa PPAR-γ on human B lymphocytes and B lymphomas was confirmed by Western blot analysis. 15-Deoxy-Δ12,14-PGJ2 (15d-PGJ2), a natural PPAR-γ agonist, has a dose-dependent antiproliferative and cytotoxic effect on normal and malignant B cells as shown by [3H]thymidine and MTT assays. Only PPAR-γ agonists (thiazolidinediones) and not PPAR-α agonists mimicked the effect of 15d-PGJ2 on B lineage cells, indicating that the mechanism by which 15d-PGJ2 negatively affects B lineage cells involves, in part, PPAR-γ. The mechanism whereby PPAR-γ agonists induce cytotoxicity is via apoptosis as shown by Annexin V staining and as confirmed by DNA fragmentation detected using the TUNEL assay. This is the first study evaluating PPAR-γ expression and its significance on human B lymphocytes. PPAR-γ agonists may serve as a counterbalance to the stimulating effects of other prostaglandins, namely PGE2, which promotes B cell immunoglobulin class switching. Finally, the use of prostaglandins such as 15d-PGJ2 and synthetic PPAR-γ agonists to induce apoptosis in B lineage cells may lead to the development of novel therapies for potentially fatal B lymphomas. [Copyright &y& Elsevier]

Mycobacterium tuberculosis is the main etiological agent of tuberculosis. The Bacillus Calmette–Guérin (BCG) microbes that are primarily used as a vaccine against tuberculosis also constitute the dominant infection model for studying the interaction of mycobacteria with the host cell types. The majority of interaction experiments have been conducted using macrophages and monocytes as prototype phagocyte cell types. Here, we report that M. bovis BCG infects mouse primary B cells as well as human B cell line. The complement receptors, along with B cell receptors, are engaged in the process of bacterial entry into the host B cells. Once inside the B cells, the intracellular trafficking of BCG follows the complete endocytic pathway of the ingested particles, which is in contrast to the events taking place during ingestion of BCG by macrophages. In vivo infection of mice with M. bovis BCG activated peritoneal as well as splenic B cells to produce proinflammatory cytokines. This paper further supports the evidence that B cells are involved in a host's early interactions with intracellular bacterial pathogens and participate in the induction of innate defense responses. • Mycobacterium bovis BCG entry B cells. • B cells are activated and produce cytokines early after BCG infection. • BCR and CRs are crucial for entry of M. bovis BCG. [ABSTRACT FROM AUTHOR]