Mouse marginal zone B cells harbor specificities similar to human broadly neutralizing HIV antibodies

作者：Pujanauski Lindsey M; Janoff Edward N; McCarter Martin D; Pelanda Roberta; Torres Raul M^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(4): 1422-1427.

DOI：10.1073/pnas.1213713110

• B-cell subsets
• virus
• germ line
• polyreactive

A series of potent, broadly neutralizing HIV antibodies have been isolated from B cells of HIV-infected individuals. VRC01 represents a subset of these antibodies that mediate neutralization with a restricted set of IGHV genes. The memory B cells expressing these antibodies were isolated years after infection; thus, the B-cell subpopulation from which they originated and the extent of participation in the initial HIV antibody response, if any, are unclear. Here we evaluated the frequency of anti-gp120 B cells in follicular (FO) and marginal zone (MZ) B-cell compartments of naive WT mice and comparable human populations in uninfected individuals. We found that in non-HIV-exposed humans and mice, the majority of gp120-reactive B cells are of naive and FO phenotype, respectively. Murine FO B cells express a diverse antibody repertoire to recognize gp120. In contrast, mouse MZ B cells recognize gp120 less frequently but preferentially use IGHV1-53 to encode gp120-specific antibodies. Notably, IGHV1-53 shows high identity to human IGHV1-2*02, which has been repeatedly found to encode broadly neutralizing mutated HIV antibodies, such as VRC01. Finally, we show that human MZ-like B cells express IGHV1-2*02, and that IGHV1-53 expression is enriched in mouse MZ B cells. These data suggest that efforts toward developing an HIV vaccine might consider eliciting protective HIV antibody responses selectively from alternative B-cell populations harboring IGHV gene segments capable of producing protective antibodies.

• 出版日期2013-1-22