Plasmodium chabaudi chabaudi Infection in Mice Induces Strong B Cell Responses and Striking But Temporary Changes in Splenic Cell Distribution

Abstract

B cells and Abs play a key role in controlling the erythrocytic stage of malaria. However, little is known about the way the humoral response develops during infection. We show that Plasmodium chabaudi chabaudi causes major, but temporary changes in the distribution of leukocytes in the spleen. Despite these changes, an ordered response to infection develops, which includes vigorous extrafollicular growth of plasmablasts and germinal center formation. Early in the response, the lymphocytes in the T zone and follicles become widely spaced, and the edges of these compartments blur. This effect is maximal around the peak of parasitemia. Germinal centers are apparent by day 8, peak at day 20, and persist through day 60. Extrafollicular foci of plasmablasts are visible from day 4 and initiate a very strong plasma cell response. Initially, the plasma cells have a conventional red pulp distribution, but by day 10 they are unconventionally sited in the periarteriolar region of the white pulp. In this region they form clusters occupying part of the area normally filled by T cells. B cells are absent from the marginal zone for at least 30 days after the peak of infection, although flow cytometry shows their continued presence in the spleen throughout infection. Relatively normal splenic architecture is regained by day 60 of infection. These results show that the changes in splenic cell distribution are linked to the presence of parasites and do not seem to interfere with the development of the humoral response.

Structural Changes in Spleen Architecture upon Plasmodium berghei (NK-65) Infection in BALB/c Mice

“…Similar observation were made by many investigator [17,18]. Accumulation of haemozoin pigment has been reported to occur due to protein degradation by parasite [19]. The present finding also indicates accumulation of haemozoin and infiltration of red blood cells in sinusoidal spaces in infected spleen.…”

The Recirculating B Cell Pool Contains Two Functionally Distinct, Long-Lived, Posttransitional, Follicular B Cell Populations

“…A likely explanation for why two distinct follicular B cell populations have evolved is that Btk-dependent BCR signals and Notch2 represent opposing inducers that respectively drive FO I B cell and MZ B cell generation, ensuring the reciprocal generation of these two distinct terminally differentiated sublineages of B-2 B cells. FO I B cells are rarely depleted in a dramatic fashion during the course of an infection, but blood-borne pathogens can cause a drastic activation and depletion of the MZ B cell pool (55,56). FO II B cells may constitute a long-lived cellular reservoir that can potentially be recruited as it transits the spleen to replenish the MZ B cell pool following a severe and acute challenge by a bloodborne pathogen.…”

Blood‐stage Plasmodium berghei infection leads to short‐lived parasite‐associated antigen presentation by dendritic cells

“…3B), indicating that the provision of DC presenting the appropriate MHC-peptide combination to prime naïve OVA-specific T cells can effectively bypass the requirement for DC to phagocytose or process the antigen in vivo. However, it is worth noting that transfer of peptide-loaded DC into P. berghei-infected mice did not fully restore T-cell responses, perhaps because of such immunoregulatory phenomena or, more likely as a result of reduced access of cells to the appropriate areas of the spleen due to alterations in spleen size and architecture that typically accompany malaria infection [15,16]. …”