Marginal zoneB cells are noncirculating mature B cells that in humans segregate anatomically into the marginal zone of the spleen and certain other types of lymphoid tissue. The spleen's marginal zone contains multiple subtypes of macrophages and dendritic cells interlaced with the MZ B cells; it is not fully formed until 2 to 3 weeks after birth in rodents and 1 to 2 years in humans. The MZ B cells within this region typically express high levels of IgM, CD21, CD1, CD9 with low to negligible levels of secreted-IgD, CD23, CD5, and CD11b that help to distinguish them phenotypically from follicular B cells and B1 B cells. In humans the splenic marginal zone B cells have evidence of somatic hypermutation in their immunoglobulin genes, indicating that they have been generated through a germinal centre reaction to become memory cells. In humans, but not rodents, marginal zone B cells are also located in the inner wall of the subcapsular sinus of lymph nodes, the epithelium of tonsillar crypts, and the sub-epithelial area of mucosa-associated lymphoid tissues including the sub-epithelial dome of intestinal Peyer's patches. Similar to B1 B cells, MZ B cells can be rapidly recruited into the early adaptive immune responses in a T cell independent manner. The MZ B cells are especially well positioned as a first line of defense against systemic blood-borne antigens that enter the circulation and become trapped in the spleen. It is believed they are especially reactive to bacterial cell wall components and self-antigens which are the products of aging. MZ B cells also display a lower activation threshold than their FO B cell counterparts with heightened propensity for plasma cell differentiation that contributes further to the accelerated primary antibody response. In specimens where the tyrosine kinase for Pyk-2 has been knocked-out, marginal zone B-cells will fail to develop while B-1 cells will still be present. MZ B-cells are the only B-cells dependent on NOTCH2 signaling for proliferation. Marginal zone B cells are the malignant cells in marginal zone lymphomas, a heterogeneous group of generally indolent lymphomas.
