Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral response

The lymphoid organs contain specialized microanatomic structures composed o f lymphoid, myeloid and stromal cells that are vital to the generation of a n effective adaptive immune response,Although the existence of these specia lized structures has been known for over a century, the developmental signa ls that generate them and the specific roles of these structures in the imm une response have remained largely elusive, Because of their position adjac ent to the marginal sinuses, marginal zone B (MZB) cells are amongst the fi rst population of cells seen by blood born antigens and are presumed to hav e a critical role in host defense against bacterial pathogens. Here we demo nstrate that a deficiency of the tyrosine kinase (Pyk-2) results in a cell autonomous defect of MZB cell production. In response to repetitive polysac charide antigens (T-independent type II (TI-II)) Pyk-2-deficient mice displ ayed marked suppression of IgM, IgG3 and IgG2a production. Furthermore, com plement receptor engagement proved necessary for the specific targeting of polysaccharide antigens to MZB cells,These results suggest how innate immun e responses mediated through complement coupling are translated into an ada ptive response by MZB cells, and provide a potential mechanism for the T ce ll independence of humoral responses to polysaccharide antigens.