Background: We compared and contrasted the dynamics of B cells subpopulations in mononuclear cells from blood, lymph nodes (LN) and intestine (INT) in progressive SIV infection of pigtailed macaques (PTMs) and in non-progressive SIV infection of African green monkeys (AGMs) to elucidate the significance of B-cell changes observed in HIV/SIV infection.
Methodology: We assessed the changes in total B cells, as well as of naive, resting, activated and tissue-like memory B-cell subpopulations using a combination of CD20, CD27 and CD21 monoclonal antibodies.The dynamics of Bregs (CD20+CD24hiCD27hiIL-10hi) were assessed by flow-cytometry. Activation, homing to the intestine, exhaustion and apoptosis status of total B cells were assessed as expression of Ki-67, TLR-2, α4β7, PD-1 and Annexin V. CD4 T follicular helper (Tfh) cells were assessed with a combination of PD1, CXCR5, ICOS and Bcl-6. Binding anti-gp41 and neutralizing antibodies were assessed in the two species.
Results: A sigificant acute loss of total circulating B cells occurred in the progressive host, followed by restoration during chronic infection. Conversely, the total circulating B cells did not significantly change in AGMs but increased in the LNs during chronic infection. A transient acute increase of B cells occurred in the gut in both species. Naive B cells decreased in all compartments in both species. Activated and resting memory B cells decreased in the blood but increased in the LNs and gut of PTMs. Circulating tissue-like memory B cells increased in blood only in PTMs, while in the gut, a similar increase was observed in both species. B cell proliferation post-SIV infection was similar in both species, the highest increases being detected in the LNs during chronic infection. Infected PTMs had elevated Bregs, which positively correlated with IL-10 xpression. PTMs had high baseline levels of α4β7, but this marker did not increased after SIV infection. Only PTMs showed significant increases in B cell activation and apoptosis. While the dynamics of both anti-gp41 and neutralizing antibodies was similar in AGMs and PTMs, rapid progressor PTMs lacked the ability to develop anti-gp41. An increase in CD4 Tfh cells was observed in the LNs, especially in PTMs.
Conclusions: In AIDS-susceptible species, but not in non-progressive hosts, SIV infection is characterized by B cell dysfunction defined by loss of total and memory B cells, increased numbers of Bregs and increased B cell activation and apoptosis. These changes do not appear to be correlated with production of neutralizing antibodies, which is similar in both species. Yet, the rapid progressor infection is associated with a severe incapacity to mount an Ab response against gp41.