LPS-Induced Migration of Peritoneal B-1 Cells is Associated with Upregulation of CXCR4 and Increased Migratory Sensitivity to CXCL12

Abstract

B-1 cells, which constitute a predominant lymphocyte subset in serosal cavities and produce most of natural antibodies, are subdivided into the CD5+ B-1a and CD5- B-1b cell subpopulations, but the differential roles of B-1a and B-1b cells are not well understood. We report that B-1a cells preferentially migrate out of the peritoneal cavity and upregulate the expression of CXCR4 with heightened sensitivity to CXCL12 and CXCL13 upon LPS treatment compared to B-1b and B-2 cells. Whereas B-1a cells were slightly more abundant than B-1b and B-2 cells in the homeostatic condition, the number of B-1a cells preferentially decreased 48 hr after LPS treatment. The decrease in the peritoneal B-1a cell number was accompanied with increased migration of B-1a cells toward CXCL-12 and CXCL-13 in in vitro transmigration assay using peritoneal B cells from LPS treated mice. The expression level of CXCR4, but not of CXCR5, was also more prominently increased in B-1a cells upon LPS stimulation. LPS-stimulated B-1a cells did not accumulate in omental milky spots in contrast to B-2 cells. These results suggest that B-1a cells actively migrate out of the peritoneal cavity through the regulation of the migratory responsiveness to chemokines and actively participate in systemic immune responses.

Characterization of Omental Immune Aggregates during Establishment of a Latent Gammaherpesvirus Infection

“…A recent study has also reported a similar observation, noting that B1-a B cells rapidly disappear from the peritoneal cavity following i.p. LPS injection and attributed this to chemokine-mediated migration toward CXCL12 and CXCL13 gradients - although only CXCR4 expression is increased on B1-a B cells while CXCR5 expression remains constant [20]. We observed a similar reduction in B1-a B cell frequency in PECs (Fig.…”

Immunological Functions of the Omentum

“…For example, infection or inflammation-driven production of IL-33 triggers the production of IL-5 by ILC2 cells, which in turn promotes the differentiation of local B1 cells in the FALCs and MS [15]. Peritoneal administration of LPS also promotes the migration of peritoneal B1 cells to the MS [50, 51, 61], where they differentiate into IgM-secreting and IgA-secreting cells, some of which colonize the intestine [67, 68], possibly by CXCR4-dependent mechanisms [69]. The omentum also supports the formation and local maintenance of IgM + memory B cells and CD11c + IgM plasmablasts in response to peritoneal infection [47].…”

Infection-induced type I interferons activate CD11b on B-1 cells for subsequent lymph node accumulation

“…CXCL13 is required for B-1 cell migration to and from the peritoneal cavity 21, 22 , whereas up-regulation of CXCR4 and corresponding CXCL12 responsiveness following LPS stimulation induced the efflux of B-1 cells from the peritoneal cavity 23 . Others showed a MyD88-dependent decrease in peritoneal B-1 cell frequencies in response to the introduction of intestinal bacteria or LPS into that site and an increase of B-1 cells in omentum and mesenteric lymphoid tissues.…”