Antibody synthesis in vitro, a marker of B cell differentiation (original) (raw)
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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
Direct interactions between B and T lymphocytes bearing complementary receptors
Journal of Experimental Medicine, 1986
A murine cloned Th cell line specific for the antigen conalbumin in the context of self I-A molecules can be activated by low concentrations of soluble antireceptor mAb. By using an antireceptor mAb to shared antigenic determinants on T cell receptors, we have shown that the ability to be activated by soluble antireceptor mAb is an unusual, although not unique, feature of this cloned T cell line. This activation does not involve occult APC, FcR, or interaction between individual cloned T cells, as limiting-dilution analysis shows that individual cells of this clone will grow in the presence of the antireceptor antibody and IL-1 as stimulus. This cloned T cell line is highly immunogenic in vivo, giving rise to antireceptor antibodies that stimulate its growth in both mice and rats. This response is not dependent upon exogenous T cells. Rather, the clone directly interacts with complementary B cells, as shown by the production of mAb in nude mice, and by production of stimulating anti...
The antibody response: A model based on antagonistic actions of antigen
Journal of Theoretical Biology, 1963
A molecular model of antibody production is presented which is based solely on selective induction. According to this model the potential to make the various antibodies is distributed randomly among immature lymphoid cells, each cell being precommitted to a limited number of antibodies. The reaction of antigen with these immature cells has two separate and antagonistic actions mediated through two separate molecular bridges between antigen and DNA. A specific stimulus occurs following a reaction of antigen with strategically located preformed antibody and results in the passage of messenger RNA from the nucleus into the cytoplasm. The net effect of the specific stimulus is maturation of the cell, with temporary production of antibody but loss of the immature cell on which specitic antibody-forming potential depends. A specific stimulus unaccompanied by a non-specific stimulus leads to acquired immunologic tolerance. However, the non-specific stimulus, which occurs through an aggregation of antibody on the surface of the antigen, results in increased multiplication of the immature cell with specific antibody-forming potential. This counterbalances the effect of maturation and leads to increased antibody-forming potential as well as to temporary production of antibody against the antigen injected.
T cell independent induction of antigen specific suppression of the antibody response
La Ricerca in clinica e in laboratorio
Immune spleen cells (from mice given 2 x 10(7) HRBC 14 days earlier) when mixed in vitro with carrier-primed syngeneic spleen cells (from mice given 2 x 10(5) HRBC 3 days earlier) are able to suppress the anti-TNP and anti-HRBC PFC response to TNP-HRBC. If immune thymocytes are substituted for spleen cells suppression is not observed. This suppression is antigen specific, resistant to anti-T treatment or x-irradiation, and is exerted by nylon wool-retained cells of the immune spleen cell population. An antigen specific suppressive factor is released from immune spleen cells in culture. Under these experimental conditions, suppression appears to be mediated by a specific product of B rather than T cells present in the immune spleen cell population.
Regulation of the Immune Response
Allergy, 1983
Anti-sheep erythrocyte antibody suppressed the in vitro CBA/H spleen cell immune response to sheep erythrocytes. This suppression required the Fc portion of antibody. Irradiated (500 tad) allogeneic Swiss spleen cells augmented the CBA/H spleen cell immune response to sheep erythroeytes. If antibody was added to cultures 24 hr after initiation of the CBA/H anti-sheep erythrocyte response in the presence of allogeneic cells, the suppression was less than when no allogeneic cells were included. On the other hand, when antibody was added at the start of the cultures rather than 1 day later, the presence of an allogeneic augmentory effect did not induce resistance to antibody feedback. The relation between the nonspeeific T cell factor (s) and antibody feedback is discussed in terms of the Fc-dependent model for antibody-mediated suppression of the B cell response to antigen.
Journal of Experimental Medicine, 1982
Contact sensitivity (CS) to 2,4-dinitrofluorobenzene (DNFB) is maximal 6 d after sensitization but declines rapidly. Previous studies have shown that this rapid decline is due to auto-anti-idiotypic (anti-Id) antibodies produced by the host. The present study was done to investigate the mechanism(s) involved in his down-regulation of the effector phase of the CS reaction. Using transfer of CS to mimic the natural effector phase, we found that the inhibition of transfer by treating DNFB-sensitized lymph node (LN) cells with either auto-anti-Id or syngeneic anti-Id serum is complement (C) independent. This inhibition requires Ia+ T cells in the immune population. Depleting immune LN cells of Ia+ T cells rendered them insensitive to inhibition by anti-Id alone, although the same population is inhibited by anti-Id plus C. This cell population is rendered sensitive to inhibited by anti-Id alone by addition of untreated DNFB-sensitized LN cells, but not by addition of normal LN cells. Fur...
Scandinavian Journal of Immunology, 1974
Bone marrow-derived (B) Iymphoq'tes are equipped with surface-bound immunoglobulin receptor molecules. The properties of these receptors (class, specificity, and affinity) are similar to tliose of the antibodies produced by the cells after antigenic stimulation (10). It is generally accepted that the first event in antigen triggering of B iymphocytes is the binding of antigenic determinants by the Ig receptors. Ail the different hypotheses advanced to explain B-cell triggering share one basic assumption, namely that the Ig receptors are directly responsible for cell activation and deliver the initial triggering signal to the cell. However, the postulated signal generated by the combination of the Ig receptor and the antigen is often insufficient for B-cell activation, and the same antigen-Ig receptor interaction can also result in paralysis. Thus, it is well known that antigen-sensitive B cells do not become activated after binding thymus-dependent antigens without the participation of several "helper mechanisms' and that they never become activated after binding haptens. To explain these findings, several hypotheses have been put forward. One of these postulates that B cells can never be triggered by binding antigen alone. Additional helper mechanisms are needed, the main one being the presence of T ceiis, which work by carrying or releasing 'associative antibodies' (I). In terms of this concept thymus-independent (TI) antigens do not exist, .ind, furthermore, an interaction between the Ig receptor and the antigen in the absence of T cells always results in paralysis. This is the most extensively worked out two-signal theory that ascribes a dominating role to T cells in the induction of immune responses. All the other two-signal hypotheses are similar in design and differ mainly in the nature of the postulated second signal (specific, specific and nonspecific, nonspecific), and, furthermore, they do not clearly propose a mechanism for tolerance induction. The main difficulty with these models is to explain how B cells can be activated by nonspecific ligands (mitogens, see later), and, consequently, this type of induction has been termed 'abnormal. Furthermore, the increasing evidence for the existence of truly thymus-independent immune responses cannot be accounted for. Another group of hypotheses does not postulate two signals for activation. Instead, it is suggested that B-cell triggering is dependent on the 'pattern' of antigenic presentation to the cell surface receptors. Macromolecules with repeated epitopes would trigger B cells directly because they would be capable of cross-linking the specific Ig receptors. Molecules with a nonrepeated structure could only activate B cells if presented to the latter in a 'locally concentrated' form. All hypotheses of this type are variants of the 'antigen concentration" model (8, 9, l6), and all suggest that T cells are active in triggering, because they concentrate the thymus-dependent (TD) antigen, either directly or via the macrophage surface, even though it is known that T cells bind less antigen and with lower stability than B cells. The actual triggering signal would always be delivered by the Ig receptors when they have been aggregated or cross-linked to a sufficient extent.