The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice.
The primary immune response of BALB/c mice to influenza (PR8) hemagglutinin (HA), a complex protein antigen, has been examined by the splenic focus assay, and the resulting monoclonal anti-HA antibodies have been characterized by their reactivity with heterologous viruses. The analysis of the primary B-cell response to HA revealed marked differences from responses previously defined for haptenic determinants. There were following differences: (a) the frequency of HA-specific B cells in both conventional and germ-free BALB/c mice was 1 in 1.0-1.5 X 10(5) splenic B cells, which is substantially lower than the frequency of B cells responsive to various simple haptenic determinants; (b) monoclonal anti-HA antibodies were predominantly of the IgA or IgM isotypes instead of IgG, which dominates antihapten responses; and (c) after immunization, the frequency of anti-HA-specific B cells increases by 10- to 50-fold, which is much greater increase than that observed after immunization with haptenic determinants. Fine specificity analysis of primary monoclonal HA-specific antibodies revealed extensive diversity and a considerable overlap with the specificities obtained from immune mice. Given the low overall frequency of HA-specific B cells, it could be calculated that the representation of most HA-specific clonotypes within the B-cell repertoire could not exceed 1 in 10(7) B cells. These findings indicate that the primary B-cell clonotype repertoire is extremely diverse and largely antigen independent in its generation.
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D005856:Germ-Free Life; D006389:Hemagglutinins, Viral; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D013154:Spleen / Q000276:immunology
D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007143:Immunoglobulin Heavy Chains