The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice.

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Abstract
The primary immune response of BALB/c mice to influenza (PR8) hemagglutinin (HA), a complex protein antigen, was examined by the splenic focus assay, and the resulting monoclonal anti-HA antibodies were characterized by their reactivity with heterologous viruses. The analysis of the primary B[bone marrow-derived]-cell response to HA revealed marked differences from responses previously defined for haptenic determinants. There were the following differences: the frequency of HA-specific B cells in conventional and germ-free BALB/c mice was 1 in 1.0-1.5 .times. 105 splenic B cells, which is substantially lower than the frequency of B cells responsive to various simple haptenic determinants; monoclonal anti-HA antibodies were predominantly of the Ig[immunoglobulin]A or IgM isotypes instead of IgG, which dominates antihapten responses; and after immunization, the frequency of anti-HA-specific B cells increases by 10- to 50-fold, which is a 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 was calculated that the representation of most HA-specific clonotypes within the B-cell repertoire could not exceed 1 in 107 B cells. The primary B-cell clonotype repertoire is extremely diverse and largely antigen independent in its generation.