Regulation of B lymphocyte replication and maturation (original) (raw)
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Journal of Experimental Medicine, 1982
We have recently reported that resting B cells must receive at least three different signals in a T helper cell (TH)-dependent as well as in a lipopolysaccharide (LPS)-induced B cell response (3), i.e., a specific TH signal (that can be bypassed by LPS), a nonspecific TH signal (mediated by Ia or antigen-nonspecific B cell helper factor), and an antigen (hapten) signal. In a system using male (H-Y) antigen-specific cloned TH of C57BL/6 origin and male (or female) B cells, we now confirm and extend these findings by demonstrating that H-Y-specific TH must see both H-Y and Ia determinants on the B cells (and not only on macrophages) to provide the first specific TH signal required for a plaque-forming cell (PFC) response. This signal was interfered with by a monoclonal anti-I-Ab antibody at the B cell level, was not mediated by detectable soluble factors (in contrast to the nonspecific signal also provided by the TH), and could be bypassed by LPS, in which case anti-I-Ab antibody had ...
Immunity Mediated by B Cells and Antibodies
The production of antibodies is the sole function of the B-cell arm of the immune system. Antibodies are useful in the defense against any pathogen that is present in the extracellular spaces of the body's tissues. Some human pathogens, such as many species of bacteria, live and reproduce entirely within the extracellular spaces, whereas others, such as viruses, replicate inside cells but are carried through the extracellular spaces as they spread from one cell to the next. Antibodies secreted by plasma cells in secondary lymphoid tissues and bone marrow find their way into the fluids filling the extracellular spaces. Figure 7.1 Cross-linking of antigen receptors is the first step in B-cell activation. The B-cell receptors (BCR) on B cells are physically cross-linked by the repetitive epitopes of antigens (Ag) on the surface of a bacterial cell. The B-cell receptor on a mature, naive B cell is composed of surface IgM, which binds antigen, and associated Iga and Igb chains, which provide the signaling capacity. B-cell receptors are activated by cross-linking with antigens Ag BCR IgM Igα, Igβ B cell signals bacterial cell 183 Antibody production by B lymphocytes
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.
The Role of I-A/E Molecules in B-Lymphoeyte Activation
Scandinavian Journal of Immunology, 1987
We have previously demonstrated ihat monuclunal anii-I-A/E antibodies inhibil B-cell responses lolipupolysiiccharide (LPS). In the present report, the inhibitory effects were shown to be carried out directly on B cells. ;ind to be totally independent of the LPS concentration used, thereby showing that anlihodies do not mediate their effect through blocking of accessory cells or stcrie hindrance of LPS-receplors. Of Ihe three different phases in B-cel! activation/ induction, proliferation, and maturation, induction was shown to be ihe most sensitive to inhibition by anti-I-A/E antibodies. Thus, kinctie studies showed that anli-LA/E antibodies are only inhibitory for the first Id h of LPS aclivation. afler whieh B cells can no longer be inhibited by these antibodies. Class II MHC molecules appear, therefore, to be pan of a nietiibrane tnolecular complex whieh regulates delivery of activation signals lo resling B ceils. Since it was also shown ihai this lime period corresponds approximately to the time required for B cells to express I'uneiional reaciivtty lo growth factors, we suggest that anti-I-A/E antibodies act on resting B lymphocytes to inhibit mitogen-dependent induction of growth receptor expression.
The Journal of experimental medicine, 1976
Although B lymphocytes can be triggered by B-cell mitogens and by certain other molecules to produce lymphokines, they do not produce lymphokines when stimulated with specific soluble protein antigens. We have investigated whether T-cell help would enable B cells to produce lymphokines when activated by antigens. Addition of small numbers of T cells to B-cell cultures resulted in significant production of a monocyte chemotactic factor. T cells could be replaced by supernates of antigen-stimulated T cells, demonstrating both that the chemotactic factor was B-cell-dervied and that T-cell help was mediated by a soluble factor. Although the T-cell factor was nonantigen specific, B-cell activation required the presence of both antigen and T-cell factor. Thus, it appears that although dependent upon T cells, B lymphocytes may play an important role in amplification of cell-mediated immune responses.
Antigen-Specific B-Lymphocyte Activation
Critical Reviews in Immunology, 2003
B lymphocytes comprise a major component of the adaptive mammalian immune system, having the exclusive ability to produce and secrete immunoglobulins (Ig) of various forms (isotypes). This property alone renders B-cell activation critical to immunity, but the fully activated B cell also functions in antigen presentation and the production of a variety of cytokines and chemokines. There are many signals that must be coordinated to achieve and properly regulate antigen-specific B-lymphocyte activation and the development of humoral memory. This review seeks to summarize these components, and to highlight recent advances in each area that contribute to a greater understanding of the complex processes involved in B-cell activation.