Changes in B Cell Populations and Merozoite Surface Protein-1-Specific Memory B Cell Responses after Prolonged Absence of Detectable P. falciparum Infection

Abstract

Clinical immunity to malaria declines in the absence of repeated parasite exposure. However, little is known about how B cell populations and antigen-specific memory B cells change in the absence of P. falciparum infection. A successful indoor residual insecticide spraying campaign in a highland area of western Kenya, led to an absence of blood-stage P. falciparum infection between March 2007 and April 2008. We assessed memory B cell responses in 45 adults at the beginning (April 2008) and end (April 2009) of a subsequent 12-month period during which none of the adults had evidence of asymptomatic parasitemia or clinical disease. Antibodies and memory B cells to the 42-kDa portion of the merozoite surface protein-1 (MSP-142) were measured using ELISA and ELISPOT assays, respectively. B cell populations were characterized by flow cytometry. From 2008 to 2009, the prevalence of MSP-142-specific memory B cells (45% vs. 55%, respectively, P = 0.32) or antibodies (91% vs. 82%, respectively, P = 0.32) did not differ significantly, although specific individuals did change from positive to negative and vice versa, particularly for memory B cells, suggesting possible low-level undetected parasitemia may have occurred in some individuals. The magnitude of MSP-142-specific memory B cells and levels of antibodies to MSP-142 also did not differ from 2008 to 2009 (P>0.10 for both). However, from 2008 to 2009 the proportions of both class-switched atypical (CD19+IgD-CD27-CD21-IgM-) and class-switched activated (CD19+IgD-CD27+CD21-IgM-) memory B cells decreased (both P<0.001). In contrast, class-switched resting classical memory B cells (CD19+IgD-CD27+CD21+IgM-) increased (P<0.001). In this area of seasonal malaria transmission, a one- year absence of detectable P. falciparum infection was not associated with changes in the prevalence or level of MSP-142 specific memory B cells, but was associated with major changes in overall memory B cell subsets.

T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response

“…We also observed involvement of T-bet + B cells in the response to HIV infection, as T-bet was rapidly induced in B cells during the acute phase and T-bet We and others have previously demonstrated an expansion of CD21 -B cell subsets induced by Th1-type human infections, including HIV, malaria, and hepatitis C (30,31,34,35,(60)(61)(62)(63), and expansion of a clonal CD21 -subset has been described during hepatitis B-and hepatitis C-associated mixed cryoglobulinemia (64)(65)(66). Interestingly, maintenance of expanded CD21 -cells in each of these infections appears to be dependent upon pathogen load (34,35,60,(67)(68)(69). Our current findings, combined with the similar CD21 -B cell phenotypes described in these studies, suggest that CD21 -B cell expansion associated with these various Th1-type infections may in part be explained by infection-induced T-bet expression and expansion of T-bet hi cells and these chronic infection-expanded CD21 -B cell subsets.…”

Apical membrane protein 1‐specific antibody profile and temporal changes in peripheral blood B‐cell populations in Plasmodium vivax malaria

“…Since humoral immune response profile in individual living in malaria endemic area is influenced by time and exposure level, we next examined changes in anti‐PvAMA‐1 IgG antibody levels and frequency of antigen‐specific MBCs at different time points after acute infection. The highest levels of antibodies to PVAMA‐1were found among CV30 subjects (63% of them had reactivity indices [RI] ≥ 1); median RI were similar among other groups.…”

cGAS-mediated control of blood-stage malaria promotes Plasmodium-specific germinal center responses

“…Antibodies against MSP1 are associated with clinical immunity in endemic populations (39,40) and murine models of Plasmodium infection (41,42). Furthermore, memory B cells specific for this protein can be found in malaria-exposed individuals living in Plasmodium endemic regions (43,44). To test the role of cGAS in the development of the humoral immune response, the differentiation of MSP1-specific B cells was assessed after P. yoelii infection of WT and cGAS -/-mice ( Figure 4A).…”