Effects of temporary BLyS treatment of rhesus macaques

Abstract

Abstract BLyS is a survival cytokine that regulates peripheral B cell numbers and transitional B cell throughput. In mice, exogenous BLyS administration yields elevated pre-immune B cell numbers, an increased proportional representation of transitional B cells, and shifts in repertoire composition (1–3). Consistent with these observations, BLyS pretreatment alters the quality of antibody responses to HIV gp140 in mice, yielding enhanced neutralizing responses (4). While it is assumed that BLyS plays analogous roles in other species, similar studies in nonhuman primates are lacking. Accordingly, we have assessed the effects of exogenous BLyS treatment in rhesus macaques. Here we treated juvenile rhesus macaques with 0.05 mg/kg recombinant human BLyS over ten days. Physical exams and blood cell counts indicate no adverse effects of treatment except a decrease in lymphocyte counts during the treatment periods. We find that the numbers and proportional representation of transitional B cells (CD20+ IgM+ CD10+) increase during and immediately following BLyS treatment, returning to pre-treatment levels within 20–30 days. There is a small increase in plasma anti-dsDNA antibody, and a significant increase in anti-recombinant human BLyS antibody indicating immunogenicity in this species. Together, these results indicate that BLyS plays similar roles in rodents and primates. They further suggest that deliberate manipulation of BLyS may be an effective approach in rhesus macaques for expanding B cell repertoire diversity and altering the quality of antibody responses.