Primary and secondary in situ antibody response: abnormal affinity maturation pattern in mice carrying the xid gene.
The xid gene in mice controls a recessive defect resulting in the absence of a late maturing subset of B cells. Whereas the responsiveness pattern of these mice have been clearly defined in terms of their ability or inability to make antibodies to certain classes of thymus-independent antigens, there are conflicting reports in regard to affinity maturation of the antibody response to thymus-dependent antigens. To resolve this controversial issue, the two major isotypes of the IgG response, namely IgG1 and IgG2a were examined with a highly sensitive radioimmunoassay that measures both the magnitude and affinity of the anti-2,4-dinitrophenyl antibody of each isotype in individual serum samples. It was found that the xid gene reduced the amount but not affinity of the IgG1 antibody produced, whereas it impaired the whole IgG2a responses severely. In fact, mice carrying the defective gene were unable to mount a secondary IgG2a response, measured either quantitatively or qualitatively in terms of increased affinity. To test the possibility that Lyb3, an isogenic B cell-triggering receptor lacking in xid-mutant mice, plays a direct role in the maturation of the immune response, the antibody profile in normal mice immunized eigher with antigen alone or in combination with anti-Lyb3 receptor substantially elevated and accelerated the primary IgG2a response, whereas it had little effect on the IgG1 response.
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D004136:Dinitrobenzenes / Q000276:immunology; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D007074:Immunoglobulin G; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA
D004136:Dinitrobenzenes; D007106:Immune Sera; D007074:Immunoglobulin G; D006433:Hemocyanins