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Abstract: Cell surface molecules are present on several lymphocyte subsets and are differentially expressed during lymphocyte development and activation. Human Leukocyte Differentiation Antigen (HLDA) Workshops have played an essential role in the identification and characterization of the molecules found in the membrane of hematopoietic cells. In the present study, the reactivities of sixty-five monoclonal antibodies (mAbs) submitted to the HLDA9 Workshop were tested. A multicolor flow cytometric analysis was performed in order to determine the expression profiles of these proteins on peripheral blood lymphocytes, hematopoietic cell lines, and tonsil B-cells. The following B-cell subsets were assessed: mature naïve, pre-germinal center, germinal center, unswitched and switched memory, plasmablasts, and plasma cells. Immunohistochemical analysis on formalin-fixed paraffin-embedded tonsils was also carried out. Remarkably, a large group of immunoglobulin family inhibitory cell surface molecules were observed on several distinct B-cell subsets including: CD152 (CTLA4), CD170 (Siglec-5), CD272 (BTLA), CD305 (LAIR1), CD307d (FCRL4), and CD329 (Siglec-9). The following molecules were also found to be differentially expressed on B-cell subsets (CD80, CD185 (CXCR5), CD196 (CCR6), CD270 (TNFRSF14), CD307a–c (FCRL1–3), CD319 (SLAMF7) and CD362 (SDC2)) or delineated B-cell subpopulations (CD126 (IL-6R), CD255 (TNFSF12), CD264 (TNFRSF10D), CD267 (TNFRSF13B) and CD329 (Siglec-9)). Of these, only CD307a, CD307b, and CD307d presented a B-cell-specific expression pattern. Our results show that several of these molecules are capable of further subdividing the known B-cell subsets and, in fact, may represent new markers for research, diagnosis, and eventually targets for the treatment of B-cell malignancies and autoimmune diseases. [Copyright &y& Elsevier]

Abstract: B cells not only play a pivotal role in humoral immunity, but also are involved in a broad spectrum of immune responses, including antigen presentation and T-cell function regulation. The identification of cell-surface CD molecules derived from a series of Human Leukocyte Differentiation Antigens (HLDA) Workshops has been instrumental to the discovery and functional characterization of human B-cell populations. Moreover, many events regulating B-cell development, activation, and effector functions are orchestrated by these cell-surface molecules. During the Ninth HLDA Workshop (HLDA9) eighteen new CDs were allocated to cell-surface molecules expressed on B cells: CD210a (IL10RA), CD215 (IL15RA), CD270 (TNFRSF14), CD307a (FCRL1), CD307b (FCRL2), CD307c (FCRL3), CD307d (FCRL4), CD351 (FCAMR), CD352 (SLAMF6), CD353 (SLAMF8), CD354 (TREM1), CD355 (CRTAM), CD357 (TNFRSF18), CD358 (TNFRSF21), CD360 (IL21RA), CD361 (EVI2B), CD362 (SDC2), and CD363 (S1PR1). Here we present their expression patterns on leukocytes, including T lymphocytes, NK cells, granulocytes, monocytes, plasmacytoid and monocyte-derived dendritic cells, and several B-cell subsets. These new CD molecules are expressed on B cells at various stages of differentiation; from bone marrow precursor pro-B cells to plasma cells. Three of them, CD307a, CD307b and CD307d, exhibit a B-cell restricted expression pattern, whereas the rest are also present on other leukocytes. In this paper we also review the structural characteristics, expression, and function of these new CD molecules. The availability of monoclonal antibodies directed against novel B cell-surface molecules will have broad implications not only for B-cell biology, but also for the development of new diagnostic and therapeutic tools. [Copyright &y& Elsevier]