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Proper regulation of B‐cell function is essential for effective humoral immunity and maintenance of immune tolerance. Here, we found that FBW7 (F‐box/WD40 repeat‐containing protein 7) is highly expressed in germinal centre B and B1 cells, and confirmed that it has an intrinsic role in maintaining homeostasis of mature B cells and B‐1 cells. FBW7 deletion led to an impairment of antibody response, and although germinal centre formation was not affected, antibody class‐switch recombination and affinity maturation processes were defective. Likewise, memory immune response was severely impaired. Moreover, FBW7 ablation ameliorated the pathogenesis of an autoimmune disease model, collagen‐induced arthritis, by reducing the production of anti‐collagen II autoantibodies. Taken together, these data suggest that FBW7 may be an attractive target for developing new therapeutics for the treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]

The maturation of immature B cells and the survival of mature B cells is stringently controlled to maintain a diverse repertoire of antibody specificities while avoiding self‐reactivity. At the molecular level this is regulated by signaling from membrane Ig and the BAFF‐receptor that sustain a pro‐survival program of gene expression. Whether and how posttranscriptional mechanisms contribute to B cell maturation and survival remains poorly understood. Here, we show that the polypyrimidine tract binding proteins (PTBP) PTBP1 and PTBP3 bind to a large and overlapping set of transcripts in B cells. Both PTBP1 and PTBP3 bind to introns and exons where they are predicted to regulate alternative splicing. Moreover, they also show high‐density of binding to 3' untranslated regions suggesting they influence the transcriptome in diverse ways. We show that PTBP1 and PTBP3 are required in B cells beyond the immature cell stage to sustain transitional B cells and the B1, marginal zone and follicular B cell lineages. Therefore, PTBP1 and PTBP3 promote the maturation of quiescent B cells by regulating gene expression at the posttranscriptional level. [ABSTRACT FROM AUTHOR]

Objective: To determine the subpopulations of B cells in peripheral blood of syphilis patients, and its association with syphilis status. Methods: Peripheral blood was taken from untreated patients with syphilis (18 cases), syphilitic serofast patients (14 cases), serological cure patients (19 cases) and normal controls (16 cases). Mature and regulatory B cells were detected by flow cytometry. Results: Compared with normal controls, the proportions of CD19+ CD24hi CD38hi regulatory B cells were significantly lower in syphilis patients (versus normal controls, untreated: t=2.10, P0.05). Conclusions: The ratio of B cell subsets is different between syphilis patient and normal controls. Proportion of mature B cells in serofast patients is abnormal, possibly due to serofast.

Objective: To determine the effect of Bryophyllum pinnatum treatment in modulating immune response and the pregnancy outcomes of pregnant pristane-induced lupus mice model. Methods: Sixteen Balb/c mice were intraperitoneally injected with single 0.5 cc pristane to induce lupus manifestations. After 12 weeks of injection, mice were mated and considered as gestational day 0 (GD0). Mice were divided into 4 groups based on the dosages of Bryophyllum pinnatum: control (no treatment), B1 (10.5 mg/kg), B2 (21 mg/kg), and B3 (42 mg/kg). The treatment was given orally every day started from GD9 until 9 days. At the end of the study, blood pressure and fetal size were measured. Serum anti-dsDNA and urine albumin levels were measured by ELISA. Spleen T helper (Th) and mature B cells percentages were measured by flow cytometry. Results: Administration of Bryophyllum pinnatum reduced the percentages of Th1 (p=0.006), Th2 (p=0.005), Th17 (p=0.000), and mature B cells (p=0.007) in dose-dependent manner. B1 and B2 had significantly lower of systolic blood pressure compared to control (p=0.026 and p=0.022 respectively). Significantly lower of anti-dsDNA levels were found in B1 group compared to control (p=0.014). However, no significantly different of urine albumin levels were found between groups. Bryophyllum pinnatum also significantly increased the fetus body weight in dose-dependent manner (p=0.000). Conclusion: Treatment of Bryophyllum pinnatum could improve the pregnancy outcome and modulate the immune response in pregnant pristane-induced lupus mice. Therefore, Bryophyllum pinnatum is a potential herb which can be developed as an immunosuppressive agent in the future.

Background: Surface immunoglobulin (sIg) light chains are not always detected on mature B cells. This may present as a challenge for clonality determination in clinical flow cytometry., Methods: To explore the mechanism and diagnostic significance of sIg negative mature B cells, we retrospectively studied 14 cases of sIg negative reactive B-cell lymphocytosis and 89 cases of sIg negative mature B-cell lymphomas. The expression patterns of sIg and cytoplasmic immunoglobulin (cIg) light chains were studied by flow cytometry using both monoclonal and polyclonal antibodies., Results: These 14 cases of sIg negative reactive B-cell lymphocytosis were proven to be polytypic based on cytoplasmic light chain studies. In 89 cases of sIg negative mature B-cell lymphomas, we described four distinct patterns of abnormal light chain expression including partial or complete loss of sIg or cIg, suggesting different underlying mechanisms., Conclusions: This study represents the first reported series of body or cystic fluids where reactive B cells do not have detectable sIg, arguing strongly against making a diagnosis of B-cell lymphoma based on lack of sIg in mature B cells. Since the lack of sIg does not always predict clonal/neoplastic mature B-cell proliferation, further cIg evaluation should be performed when sIg expression is not detected in mature B cells. The lack of both sIg and cIg in mature B cells may serve as a reliable surrogate clonality/neoplastic marker., (© 2022 International Clinical Cytometry Society.)

Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by T and B cells. It is characterized by a variety of autoantibodies and systemic clinical manifestations. A tolerogenic peptide, designated hCDR1, ameliorated the serological and clinical manifestations of SLE in both spontaneous and induced models of lupus. In the present study, we evaluated the status of mature B cells in the bone marrow (BM) of SLE-afflicted mice, and determined the effect of treatment with the tolerogenic peptide hCDR1 on these cells. We demonstrate herein that mature B cells of the BM of SLE-afflicted (New Zealand Black × New Zealand White)F1 mice were largely expanded, and that treatment with hCDR1 down-regulated this population. Moreover, treatment with hCDR1 inhibited the expression of the pathogenic cytokines [interferon-γ and interleukin (IL)-10], whereas it up-regulated the expression of transforming growth factor-β in the BM. Treatment with hCDR1 up-regulated the rates of apoptosis of mature B cells. The latter was associated with inhibited expression of the survival Bcl-xL gene and of IL-7 by BM cells. Furthermore, the addition of recombinant IL-7 abrogated the suppressive effects of hCDR1 on Bcl-xL in the BM cells and resulted in elevated levels of apoptosis. Hence, the down-regulated production of IL-7 contributes to the hCDR1-mediated apoptosis of mature B cells in the BM of SLE-afflicted mice. [ABSTRACT FROM AUTHOR]

We examined the expression of recombination-activating genes (RAG-1 and RAG-2) and activation-induced cytidine deaminase (AID) by mature human blood B cells stimulated with anti-CD40 in the presence of IL-4 or IL-13. IL-4 was an effective cofactor for RAG-1 and RAG-2 expression, whereas IL-13 was not. In addition, IL-4-dependent RAG expression combined with AID and IgE expression allowed predominant expression of newly rearranged λ light chains on IgE+ cells generated from κ+ cells. Although the magnitudes of IL-4- and IL-13-dependent AID and IgE expression were related to expression levels of binding subunits of the IL-4 and IL-13 receptors, IL-13 was ineffective for light chain replacement in the induced IgE+ cells due to the failure in RAG expression. Our studies using mature blood B cells indicate that IL-4-responsive cells, unlike IL-13-responsive cells, undergo λ gene rearrangement leading to replacement in parallel with RAG expression and suggest that this replacement may contribute to the regulation of affinity maturation of IgE antibodies. [Copyright &y& Elsevier]

The IL-2/IL-2 receptor (IL-2R) has been studied intensively because of its potential function in the development and regulation of the immune system. The IL-2Rα chain has been shown to be expressed on CD4minus; thymocytes and activated T and B cells. In this report, we show that IL-2Rα is also expressed on precursor B cells in the bone marrow. Its expression is initiated by functional rearrangement and expression of Ig μ heavy chain gene and is down-regulated when immature B cells mature and express IgD. Its potential function in early B cell differentiation is discussed in comparison with its role in thymocyte differentiation. [ABSTRACT FROM PUBLISHER]

Activation process of mature B cell is predominantly driven by specific BCR-mediated pathways, switched on and off all through late B cell differentiation stages. Mice deficient for APS, a member of the Lnk/SH2B family of adaptor proteins, showed that this adaptor plays a BCR-mediated regulatory role in mature B cells. However, the intermediates involved in this adaptor modulating functions in B cells are still unknown. In the present study, we investigated the role of APS in regulating BCR signalling notably through cytoskeleton remodeling in mature B cells. Herein, we showed that APS function is stage specific, as it exclusively intervenes in mature B cells. Upon activation, APS colocalizes with the BCR and associates with important regulators of BCR signalling, such as Syk and Cbl kinase. Importantly, APS interferes, as a scaffold protein, with the stability of Syk kinase by recruiting Cbl. This function is mainly mediated by APS SH2 domain, which regulates BCR-evoked cell dynamics. Our findings thus reveal that APS plays a regulatory role in BCR-induced responses by specifically modulating its interacting partners, which positions APS as a relevant modulator of BCR signalling in mature B cells. • APS, a SH2B adaptor protein, plays a stage specific regulatory role in BCR- mediated signaling in mature B cells. • The adaptor interferes with cytoskeleton remodeling by regulating the stability of the Syk kinase in the early signalosome. [ABSTRACT FROM AUTHOR]