Intestinal B cell hyperactivity in AIDS is controlled by highly active antiretroviral therapy

Antigen-Dependent and -Independent Mechanisms of T and B Cell Hyperactivation during Chronic HIV-1 Infection

“…HIV infection is associated with severe B cell disturbances (105), and memory B cell responses are reported to be impaired, particularly in the context of vaccinations (31,64,97,111,117). Hyperactivation of B cells during untreated chronic HIV-1 infection is also part of these disturbances and is characterized mainly by increased expression of surface activation markers, increased polyclonal B cell activation, increased cell turnover, increased frequencies of plasmablasts, and manifestation of hypergammaglobulinemia (31,88,89,105,111,129).…”

“…Hyperactivation of B cells during untreated chronic HIV-1 infection is also part of these disturbances and is characterized mainly by increased expression of surface activation markers, increased polyclonal B cell activation, increased cell turnover, increased frequencies of plasmablasts, and manifestation of hypergammaglobulinemia (31,88,89,105,111,129). The extent of HIV-associated hypergammaglobulinemia and B cell activation is not exclusively linked to HIV specificity, as less than 20% of Ig-secreting B cells have been shown to be specific for gp160 and less than 10% specific for p24 (129).…”

“…Since microbial translocation from the GI tract is systemic (at least in SIV-infected macaques [40]) and has been closely linked to chronic T cell activation in HIV infection, it is conceivable that it also impacts systemic B cell hyperactivation, perhaps even in an antigen-dependent manner. Indeed, HIV-associated B cell disturbances have been observed not only systemically but also locally in the HIV-infected gut, evidenced by intestinal B cell hyperactivity, destruction of gastrointestinal germinal centers, and intrafollicular impairment of the immunoglobulin switch enzyme activationinduced deaminase (AID) (91,111,155). Whether HIV-associated enteropathy and increased systemic exposure to GI tract microbial antigens contribute to HIV-associated hypergammaglobulinemia in an antigen-dependent manner was recently addressed (60).…”

The Mucosal B Cell System

“…intestinal B cell system has received less attention ( Figure 26). Our study provided evidence of immunological hyperactivity in that IgA + and IgG1 + PCs were significantly increased in the duodenum of AIDS patients and HAART could largely reverse this perturbation (Nilssen et al, 2004). Other abnormalities of the intestinal B cell system have also been described in AIDS (Costiniuk and Angel, 2012), and inadequate T FH cell function may impair SHM and thereby the production of high-affinity SIgA antibodies (Cubas et al, 2013).…”

“…However, it has been shown that macrophages infected with HIV-1 transfer the immunosuppressive protein negative factor Nef by conduits to B cells in GCs of GALT, thereby blocking intrafollicular AID expression and CSR . Despite this suppression of T-cell-dependent immune responses, it is known that intestinal production of IgA and IgG may be maintained or increased in patients infected with HIV-1 (Nilssen et al, 2004). This may be explained by T-cell-independent CSR generating low-affinity antibodies, because…”