Role of Mzb1 in peripheral B cell subsets
Peripheral B lymphocytes consist of multiple cell populations that differ in their phenotype, functional properties and anatomic locations. In addition to the vast majority of conventional B cells, also termed follicular B cells, which resides in lymph nodes and follicles of the spleen, marginal zone B cells occupy the marginal sinus of the spleen, and B1 cells are predominantly found in the peritoneal pleural cavities. B1 cells and marginal zone B cells have been termed ‘innate-like B cells’ because these cells quickly differentiate into antibody-secreting cells that produce ‘natural,’ polyreactive antibodies. Therefore, these cells are considered to bridge the innate and adaptive immune responses.
Previously, we identified and cloned a gene, termed Mzb1, which is abundantly expressed in marginal zone B cells and B1 cells. Mzb1 is an endoplasmic reticulum-localized protein that regulates antibody secretion, calcium homeostasis and integrin-mediated cell adhesion. In particular, Mzb1 function is required under conditions of ER stress that occurs naturally during plasma cell differentiation and under conditions of DNA damage. Mzb1 interacts with the chaperone Grp94 and seems to act as a substrate-specific co-chaperone. Current efforts focus on the mechanism by which Mzb1 regulates functions specific to innate-like B cells.