B cell subpopulations alteration in pathogenic and nonpathogenic SIV infections (VIR7P.1061)

Abstract

Abstract SIV/HIV infection is associated with B cell dysfunction, the significance of which is not known. We compared the B cell dynamics in blood, lymph nodes (LNs) and gut during SIVsab pathogenic infection of pigtailed macaques (PTMs) and nonprogressive SIVsab infection of African green monkeys (AGMs) by monitoring the B cell subsets, B regulatory cells (Bregs), CD4+ T follicular helper (Tfh) cells, B cell immune activation, apoptosis, exhaustion and homing to the intestine. Binding anti-gp41 and neutralizing antibodies (Nabs) were also measured. Acute SIV infection induced a transient but significant loss of total circulating B cells in PTMs only. In AGMs, total B cell from LNs increased during chronic infection. B cells transiently increased in the gut and naïve subset decreased in all three compartments in both species. Memory B cell subsets showed a different dynamic for both species. Bregs increased in PTM, correlated with IL-10 expression. B cell proliferation occurred in both species. PTMs expressed high baseline levels of α4β7, high degree of B cell activation and apoptosis and high frequency of Tfh. The dynamics of Ab response was similar in both species, but rapid progressor PTMs lacked the ability to mount anti-gp41. Our data show that B cell dysfunction only occurs in pathogenic SIV infection. While B cell changes were not correlated with production of Nabs, rapid disease progression associated a severe incapacity to mount an anti-SIV Ab response.