Antibody feedback and somatic mutation in B cells: regulation of mutation by immune complexes with IgG antibody.
In response to an appropriate antigenic stimulus, and with help from T lymphocytes, naive B cells differentiate into plasmacytes which produce the primary (germline-encoded) IgM and IgG antibody with low affinity for the antigen. The isotype switch from IgM to IgG coincides with the burst of germinal center reaction and the onset of somatic hypermutation. Here we propose that formation of immune complexes between the residual antigen and the primary IgG antibody, which activate complement and localize specifically in the network of follicular dendritic cells, provides an important signal for triggering the mutation mechanism in germinal center B cells. This hypothesis has been supported by studies on immunogenicity of immune complexes in vivo. The experiments have included an immunization with pre-formed antigen/IgG antibody complex and/or an administration of IgG antibody shortly after the antigen injection. Either of these strategies, which are known to augment the germinal center formation, resulted in earlier onset of somatic mutation and increased mutation frequency in VDJ rearrangements in antigen-reactive B cells, provided that help from T cells was also present. It is presumed that the antigen/antibody/complement complex is able to deliver this important signal by cross-linking of antigen receptor with the CD21/CD19/CD81 molecules on B cells. As a corollary, the signaling by immune complexes may lower the threshold of cell activation determined by receptor affinity for antigen and stimulate diverse V-gene repertoire of B-cell clones in germinal centers.
Song
H
H
Department of Microbiology and Immunology, University of Maryland, Baltimore 21201, USA.
Nie
X
X
Basu
S
S
Cerny
J
J
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics* / Q000276:immunology; D000916:Antibody Diversity / Q000235:genetics* / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000235:genetics* / Q000276:immunology; D009154:Mutation
D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; C048844:anti-IgG