Studies on non-H-2-linked lymphocyte-activating determinants (original) (raw)
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Heterogeneity of human B lymphocytes as revealed by monoclonal antibodies
Annales De L'institut Pasteur. Immunologie, 1984
Two monoclonal antibodies directed at determinants on human B lymphoeytes were produced and characterized by indirect immunofluorescence. The antibodies, BL13 and BL14, were found to be specific for B cells, since they did not react on red cells, platelets, granulocytes, monocytes or T lymphocytes. BL14-associated antigen was present on most of the circulating and tissular B cells, whereas that detected by BL13 was mainly restricted to a subpopulation preferentially homed in germinal centers of secondary follicles of lymph nodes and tonsils, which did not circulate under normal conditions and disappeared once B cells were activated by mitogens. Immunoprecipitation studies demonstrated that BL13 precipitated an antigen of approximately 160,000 d. Pathological studies confirmed the specificity of BL13 and BL14 antibodies for B lymphocytes, since they never reacted with non-B malignancies. BL14 bound to nearly all malignant B-cell proliferations except very immature and plasmacytoma cells. In contrast, BL13 was always found to be negative on acute lymphocytic leukaemias, prolymphocytic leukaemias, hairy cell leukaemias and plasma cells, whereas it detected 40-50% of chronic lymphocytic leukaemias and Burkitt or non-Burkitt lymphomas. These results led us to hypothesize several compartments for B-lymphocyte differentiation, either in central (bone marrow) or peripheral lymphoid organs, with BL13 antibody defining one compartment in the germinal centers.
The Antibody Repertoire of Early Human B Cells
Scandinavian Journal of Immunology, 1990
Our previous studies have shown that a high frequency of Epstein-Biirr virus (EBV)-immorlalized cord blood (CB) and feliil liver (FL) clones produce IgM aniibodies which display extensive autoreaclivity for IgG Fc (rheumatoid factor. RF), To investigate further the repertoire ofthese early B cells, we have examined ihe expression of C"RI associated with RFparaproteinsin relation to antibody specificity and polyreactivity. CRI were detected by ELISA and.or flow cytometry using a panel of well-charactcri/cd monoclonal antibodies detining idiotopes associated with particular V^ and Vn gene family products and raised against Fc-specitic paraproteins. Many of the CRI were expressed by these clones, suggesting that they may be markers of early B cells. The presence of the CRI was not always associated with Fc specificity. Three of eight CB FL clones expressed the VJIl subgroup of light chains, and two of these expressed the VJIl subsubgroup associated CRL 17-109, These two clones reacted with IgG Fe, and one also hound to single-stranded DNA, The VnIll-associated idiotope DI2 was expressed on IgM from 4 out of 9 FL and 3 out of !2 CB clones, D12 and B6 (also a Vn-III-associated CRI) were coexpressed in 4 out of 5 CB clones but not in the four FL clones. Seven out of nine clones expressing these idiotopes were polyreactive. and tive had Fc-binding activity. Three of the 12 CBclones expressed the V^ I-assoeiatedconformationa I idiotope G8, One of 20 CLL clones expressed both B6 and D12, and another expressed both 17-109 and the Vulassociated G6 and GS idiotopes. Taken together, these data provide evidence for the Irequenl usage, in early B cells, of V^ subgroups and V||-associated idiotopes of RF paraproteins. The expression of these CRI was not a prerequisite for binding to IgG Fc. but there was a Irequenl association ofthese idiotopes with it, DilTerences in expression of CRI between CLL and early B-cell clones may suggest differences in the pattern of VH usage between these subsets of B cells.
The "Ly-1 B" cell subpopulation in normal immunodefective, and autoimmune mice
Journal of Experimental Medicine, 1983
Since the distinction was made between immunoglobulin-bearing (B) lymphocytes that give rise to antibody forming cells and thymus derived, Thy-l-bearing (T) lymphocytes responsible for a host of other immune functions, substantial effort has been directed toward finding individual cell surface markers that subdivide these populations. In the mid-1970s, the Lyt-1, Lyt-2, and Lyt-3 antigens were shown (with the assays then available) to be represented exclusively on T cells (1, 2) and to identify functionally distinct T cell subpopulations. Lyt-1 appeared to be restricted to the helper-amplifier subset, and Lyt-2 and Lyt-3 defined the suppressor-cytotoxic subset (3-6).
Journal of Experimental Medicine, 1979
Lyb 5 is a B-cell alloantigen which is expressed on 50-60% of B cells. It was defined originally on the basis of cytotoxicity. We have described a new reactivity within the anti-Lyb 5 serum on the basis of selective inhibition of antibody responses in vitro by this antiserum in the absence of complement. This inhibitory activity of anti-Lyb 5.1 serum appears to be due to recognition of antigenic determinants different from the prototype antigens detected in the cytotoxicity assay. Anti-Lyb 5 serum incorporated into spleen cell cultures selectively inhibits antibody responses to a class of thymus-independent antigens (TI-2) previously characterized by their failure to elicit antibody formation in immature mice or in the defective CBA/N strain. Responses to optimal concentrations of TI-1 antigens, which can induce antibody synthesis in these mice, are unaffected by the addition of anti-Lyb 5.1 serum. The B-cell alloantigen defined by this functional assay is designated tentatively Lyb...
Regulation of B-Lymphocyte Activation, Proliferation, and Differentiation
Annals of the New York Academy of Sciences, 1987
Lymphocyte growth and differentiation are controlled by signals resulting from the interaction of antigen and cellular products, such as lymphokines, with specific cell membrane receptors. Resting B lymphocytes can be activated by low concentrations (l-5 &ml) of antibodies to membrane IgM, which is the B-lymphocyte receptor for antigen. The binding of anti-IgM to B cells causes a rapid increase in intracellular free calcium concentration ([Ca"]i), in inositol phosphate concentration, and in protein kinase activity. Moreover, the effects of anti-IgM on B cells are mimicked by the combined use of calcium ionophores and phorbol esters. Since phorbol esters activate protein kinase c, this suggests that the increase in [Ca*']i and in phosphatidylinositol metabolism stimulated by anti-&M are critical events in B-cell activation. The entry into S phase of B cells stimulated with anti-IgM depends on the action of a T-cell-derived factor designated B-cell stimulatory factor (BSF)-1. This is a 20,000-Da protein which is a powerful inducer of class II major histocompatibility complex molecules. Although an important cofactor for B-cell proliferative responses to anti-IgM, its major locus of action is on resting B cells. B cells stimulated with anti-IgM and BSF-1 do not synthesize secretory IgM. However, if two additional T-cellderived factors, B 15 I-TRF and interleukin-2, are added to cultures, a substantial proportion of stimulated B cells produce secretory IgM. BSF-1 has also been shown to participate in the "switch" in Ig class expression. Resting B cells cultured with lipopolysaccharide will switch to IgG, secretion in the presence of purified BSF-1.