B cell repertoire diversification precedes immunoglobulin receptor expression.

68 monoclonal antibodies specific for the hemagglutinin (HA) of the influenza virus, PR8, were obtained from sIg- bone marrow B cell precursors stimulated in splenic fragment cultures. Reactivity pattern (RP) analysis demonstrated that these anti-HA antibody responses included at least 29 distinguishable clonotypes. Comparison of the specificities of anti-HA antibodies obtained from sIg- bone marrow cells with those obtained from adult spleen cells indicates that the anti-HA repertoires of the two populations are comparable in diversity. Since the sIg- bone marrow B cell precursor pool presumably has not encountered V region-specific regulatory mechanisms in vivo, our data suggest that substantial diversification of the B cell repertoire precedes surface immunoglobulin (sIg) expression and subsequent interaction with environmental regulatory processes.