title: Mouse marginal zone B cells harbor specificities similar to human broadly neutralizing HIV antibodies.
abstract: 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 naïve 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 naïve 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.
authors.affiliation: Integrated Department of Immunology, University of Colorado School of Medicine, Denver, CO 80206, USA.
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Pujanauski
authors.forename: Edward N
authors.initials: EN
authors.lastname: Janoff
authors.forename: Martin D
authors.initials: MD
authors.lastname: McCarter
authors.forename: Roberta
authors.initials: R
authors.lastname: Pelanda
authors.forename: Raul M
authors.initials: RM
authors.lastname: Torres
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D050438:Genes, Immunoglobulin Heavy Chain; D015483:HIV Antibodies / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007143:Immunoglobulin Heavy Chains