The peritoneal micromilieu commits B cells to home to body cavities and the small intestine.

The distinct combination of homing receptors such as selectins, chemokine receptors, and integrins directs the migration of lymphocytes throughout the body. Upon activation lymphocytes irreversibly switch their set of homing receptors, now guiding them to entirely different destinations. Here we report that exposure of naive B cells to the microenvironment of the peritoneal cavity modulates their migration propensities in the absence of antigenic stimulation. B1 and B2 cells isolated from the peritoneal cavity reenter this compartment more efficiently compared with splenic follicular B cells. Moreover, when kept in the peritoneal cavity splenic follicular B cells gain such increased capability to reenter this compartment. These altered migratory capacities are reflected by an up-regulation of the chemokine receptors CXCR4 and CXCR5 and beta7 integrin by the peritoneum-experienced splenic B cells, among which CXCR5 is instrumental in directing B cells into the peritoneal cavity. Moreover, intraperitoneal transfer of plasma blasts favors their migration into the small intestine presumably before class switch recombination occurs, demonstrating that a reconfigured transient migration pattern is not restricted to naive cells. In conclusion, these data demonstrate a hitherto unrecognized role for tissue-specific cues, altering the migratory capacity of B1, naive B2, as well as antigen-experienced B2 cells.