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.
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1 March 1978
Article|
March 01 1978
The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice.
M P Cancro
W Gerhard
N R Klinman
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1978) 147 (3): 776–787.
Citation
M P Cancro, W Gerhard, N R Klinman; The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice.. J Exp Med 1 March 1978; 147 (3): 776–787. doi: https://doi.org/10.1084/jem.147.3.776
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