Figure 3

MZ B-cells shuttle between the MZ and follicles and transport Ag and pathogens to follicular DC. In steady-state conditions, strong expression of LFA1 and α4β1 integrins and receptors 1 and 3 of Sphingosine 1-Phosphate (S1P) on MZ B-cells, together with high levels of S1P in blood, contributes to the retention of MZ B-cells within the MZ. Type I IFN produced in response to blood-borne pathogens inactivates S1P1 and 3, allowing MZ B-cells to migrate in response to CXCL13, which is highly expressed in follicles. During this relocation, MZ B-cells can transport immune complexes bound to non-BcR receptors and deliver them to follicular DC (FDC). Once on FDC, these import Ags participate in the adaptive Ab response[56, 83]. Rapid ligand-induced desensitisation of CXCR5 authorizes MZ B-cells to return to the MZ. Overproduction of BAFF, which preferentially increases the chemotaxis of CD27+ MZ and memory B-cells to CXCL13 might also impair this shuttling and lead to prolonged sequestration of MZ B-cells within follicles[86]. Such a mechanism would be at work during acute infection by SIV, where it might favour sequestration of activated B-cells within follicles[82].