The analysis of the monoclonal immune response to influenza virus. III. The relationship between stimulation of virus-primed precursor B cells by heterologous viruses and reactivity of secreted antibodies.

Individual splenic precursor B cells from BALB/c mice primed with influenza virus PR8[A/PR/8/34 (H0N1)] were stimulated in vitro in the splenic fragment culture system by homologous or various heterologous influenza viruses. The specificity of the stimulated precursor cells was determined by analysis of the antibodies secreted by the ensuing plasma cell clone in a radioimmunoassay (RIA). Viruses of the H2N2 and H3N2 subtypes were unable to stimulate hemagglutinin (HA)- or neuraminidase (NA)-committed precursor B cells but did efficiently stimulate chicken host component (ChHC)-committed precursors. Viruses of the H1N1 and H0N1 subtypes could stimulate precursors committed to any of the three viral surface components. Analysis of the fine specificity of HA-committed B cells showed that BEL(H0N1) and CAM(H1N1) stimulated almost exclusively precursors whose clonal antibody product reacted with the stimulating virus in the RIA. On the other hand, WSE and MEL (both H0N1) quite frequently were able to stimulate precursors whose clonal antibody product did not react with the stimulating virus in the RIA. These results suggest that the stimulatory interaction of viruses with the cell-bound immunoglobulin receptors is slightly less affinity dependent than the antigen-antibody interaction in the RIA.