Bound C3 as the second signal for B-cell activation

Dukor, P.; Hartmann, Klaus-Ulrich

doi:10.1016/0008-8749(73)90199-8

Cited by 145 publications

(57 citation statements)

References 54 publications

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“…An alternative recent hypothesis is that C3 binding to B-cell C3 receptors constitutes an obligatory second signal for triggering which B cells must receive in addition to specific recognition of T-dependent or T-independent antigens (52,53). It has also been suggested that the interaction of "activated" C3 with B cells is mitogenic per se (52,53).…”

Section: Discussionmentioning

confidence: 99%

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Role of Complement in Induction of Antibody Production in Vivo

Pepys

1974

The Journal of Experimental Medicine

310

105

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There has been considerable recent progress in understanding of the mechanisms involved in cooperation between T and B lymphocytes in the induction of humoral antibody formation (see for example 1), but much still remains to be learned. The discovery of an interaction between lymphocytes and the fixed C3 component of complement (2-5), and the demonstration by Nussenzweig et al. that C3 receptors are a feature of B-cell populations (6-10), raise the possibility that C3 might play a part in this process (11). Germinal centers of lymphoid tissue, in which the induction of antibody production m a y occur, contain B cells, fixed C3, and complexes capable of fixing C3 (12). I have previously shown that treatment of mice in vivo with the C3-cleaving protein of cobra venom (CoF) 1 suppresses thymus-dependent but not thymus-independent antibody production, suggesting a possible role for C3 in lymphocyte cooperation (11).

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Section: Discussionmentioning

confidence: 99%

“…It has also been suggested that the interaction of "activated" C3 with B cells is mitogenic per se (52,53). Direct testing has, however, demonstrated the complement independence of B-cell triggering by mitogens (54).…”

Section: Discussionmentioning

confidence: 99%

Role of Complement in Induction of Antibody Production in Vivo

Pepys

1974

The Journal of Experimental Medicine

310

105

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“…Alternatively, it has been proposed that B-lymphocyte activation requires the interaction of that cell both with specific antigen and with another ligand leading to the generation of two signals within the cell. A major candidate for the ligand generating the so-called "second signal" would be activated C3 binding to to the C receptor (5). In such a model the binding of activated C3 would be crucial to B-cell stimulation.…”

Section: (From the Laboratory Of Immunology And The Laboratory Of CLImentioning

confidence: 99%

Ontogeny of B Lymphocytes

Gelfand

Elfenbein

Frank

et al. 1974

The Journal of Experimental Medicine

121

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The class of mammalian lymphocytes equivalent to the bursa-derived (B) 1 lymphocytes of birds may be identified by the presence of large amounts of immunoglobulin (Ig) on the surface of most of these cells (1, 2). In addition, many of these B lymphocytes, but not thymus-derived (T) lymphocytes, bear a surface receptor for an activated component of C3 allowing them to bind antigen-antibody-complement complexes (3). These cells are referred to as complement receptor lymphocytes (CRL).Although no functional role for the C receptor of B lymphocytes has yet been established, at least two major possibilities have been suggested. Firstly, the C receptor by binding antigen-antibody-complement complexes may serve as an antigen concentrating mechanism and thus increase the likelihood that antigens would interact with with specific receptors on the surface of immunocompetent B lymphocytes and then activate these cells (4). Alternatively, it has been proposed that B-lymphocyte activation requires the interaction of that cell both with specific antigen and with another ligand leading to the generation of two signals within the cell. A major candidate for the ligand generating the so-called "second signal" would be activated C3 binding to to the C receptor (5). In such a model the binding of activated C3 would be crucial to B-cell stimulation.

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“…In addition, C3, and especially C3b, have been implicated as mediators in the stimulation of antibody-forming cells (13,14).…”

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Third component of complement (C3): structural properties in relation to functions.

Bokisch¹,

Dierich²,

Müller‐Eberhard³

1975

Proc. Natl. Acad. Sci. U.S.A.

110

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The third component of complement (C3) fulfills a pivotal role in the functions of the complement system. We have investigated the topological relationships among its polypeptide chains, physiologic fragments, enzyme attack regions, and functional sites. C3 consists of two chains (a and ,6) which are linked by disulfide bonds and noncovalent forces and which have molecular weights of, respectively, 120,000 and 75,000. C3 is activated by action of C3 convertase on the a-chain. With hydrolysis of one polypeptide bond, C3a, the 9000 dalton activation peptide is dislocated from the NH2-terminal portion of the a-chain. A previously concealed binding region is thereby transiently revealed in the C3b-fragment (181,000 dalton) which displays affinity for apparently nonspecific acceptors present on biological membranes. Binding of nascent C3b to membranes occurs through the C3d portion of the fragment because subsequent action of the C3b-inactivator or trypsin on bound C3b causes release of C3c, but not of C3d. Bound C3b and C3d possess stable sites that are capable of binding to specific receptors present on a limited variety of cells. We propose that all known physiologically occurring fragments of C3 arise by enzymatic cleavage of the a-chain: C3a, C3b, C3c, and C3d. Whereas C3a (a,) and C3d (a2) consist of a single chain and C3b consists of two chains (a' and ,B), C3c is composed of the entire ,3-chain and multiple fragments of the a-chain, each of which is linked by disulfide bonds to the ,3-chain.The aim of this communication is to describe the topological relationships among chains, fragments, functional sites, and enzymatic attack regions of the C3 molecule (third component of complement).C3, which was first recognized and isolated in 1960 (1), fulfills multiple physiological functions in host defense against pathogenic microorganisms and probably transformed host cells. It occurs in plasma and in other body fluids in inactive, but activatable form. The activating enzyme, C3 convertase or C4,2, cleaves the molecule into two fragments, C3a and C3b (2, 3). The activation peptide, C3a, constitutes one of the two known anaphylatoxins. In very low concentrations the peptide effects release of histamine from mast cells (4), chemotactic migration of polymorphonuclear leukocytes (3, 5), and contraction of smooth muscle (2,3,6). In vivo it is phlogogenic and causes formation of cutaneous edema and erythema (7,8).The large fragment, C3b, in its nascent state, is capable of binding to the surface of cells (9) For this purpose fresh human serum containing 0.05% NaN3 was incubated for 5 days at 370, under which conditions C3 is degraded and these fragments accumulate. Alternatively, 250 ml of fresh human serum was incubated at 370 for 1 hr with 2 mg of isolated cobra venom factor (26) and was subsequently held at 40 overnight. C3c and C3d were isolated by a threestep procedure. Treated serum (250 ml) was dialyzed against phosphate buffer, pH 8.1, having a conductance of 4 mmho/ cm. The serum was applied to a 3-lit...

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Bound C3 as the second signal for B-cell activation

Cited by 145 publications

References 54 publications

Role of Complement in Induction of Antibody Production in Vivo

Role of Complement in Induction of Antibody Production in Vivo

Ontogeny of B Lymphocytes

Third component of complement (C3): structural properties in relation to functions.

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