B Cell Responses Associated with Vaccine-Induced Delayed SIVmac251 Acquisition in Female Rhesus Macaques

An established sex bias in HIV pathogenesis is linked to immune responses. Recently we reported a vaccine-induced sex bias: vaccinated female but not male rhesus macaques exhibited delayed SIV acquisition. This outcome was correlated with SIV Env–specific rectal IgA, rectal memory B cells, and total rectal plasma cells. To uncover additional contributing factors, using samples from the same study, we investigated memory B cell population dynamics in blood, bone marrow, and rectal tissue during immunization and postchallenge; IgG subtypes and Ab avidity; and regulatory B (B reg ) cell frequency and function. Few sex differences were seen in Env-specific memory B cell, plasmablast, or plasma cell frequencies in the three compartments. Males had higher IgG Ab titers and avidity indices than females. However, females had elevated levels of Env-specific IgG1, IgG2, and IgG3 Abs compared with males. gp140-specific IgG3 Abs of females but not males were correlated with Ab-dependent cell-mediated cytotoxicity activity against gp120 targets ( p = 0.026) and with Ab-dependent phagocytic activity ( p = 0.010). IgG3 Ab of females but not males also correlated with decreased peak viremia ( p = 0.028). Peripheral blood CD19 + CD25 + B reg cells suppressed T cell proliferation compared with CD19 + CD25 − cells ( p = 0.031) and exhibited increased IL-10 mRNA expression ( p = 0.031). Male macaques postvaccination ( p = 0.018) and postinfection ( p = 0.0048) exhibited higher B reg frequencies than females. Moreover, male B reg frequencies correlated with peak viremia ( p = 0.0071). Our data suggest that vaccinated females developed better Ab quality, contributing to better functionality. The elevated B reg frequencies in males may have facilitated SIV acquisition.