are responsible for generating the majority of high-affinity antibodies during an infection. marginal-zone (mz) b cellfound mainly in the marginal zone of the spleen and serves as a first line of defense against blood-borne pathogens, as the marginal zone receives large amounts of blood from the general circulation. they can undergo both t cell-independent and t cell-dependent activation, but preferentially undergo t cell-independent activation. b-1 cellarises from a developmental pathway different from fo b cells and mz b cells. in mice, they predominantly populate the peritoneal cavity and pleural cavity, generate natural antibodies (antibodies produced without infection), defend against mucosal pathogens, and primarily exhibit t cell-independent activation. a true homologue of mouse b-1 cells has not been discovered in humans, though various cell populations similar to b-1 cells have been described. regulatory b (breg) cellan immunosuppressive b cell type that stops the expansion of pathogenic, pro-inflammatory lymphocytes through the secretion of il-10, il-35, and tgf-β. also, it promotes the generation of regulatory t (treg) cells by directly interacting with t cells to skew their differentiation towards tregs. no common breg cell identity has been described and many breg cell subsets sharing regulatory functions have been found in both mice and humans. it is currently unknown if breg cell subsets are developmentally linked and how exactly differentiation into a breg cell occurs. there is evidence showing that nearly all b cell types can differentiate into a breg cell through mechanisms involving inflammatory signals and bcr recognition. b cell-related pathology autoimmune disease can result from abnormal b cell recognition of self-antigens followed by the production of autoantibodies. autoimmune diseases where disease activity is correlated with b cell activity include scleroderma, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes, post-infectious ibs, and rheumatoid arthritis. malignant transformation of b cells and their precursors can cause a host of cancers, including chronic lymphocytic leukemia (cll), acute lymphoblastic leukemia (all), hairy cell leukemia, follicular lymphoma, non-hodgkin's lymphoma, hodgkin's lymphoma, and plasma cell malignancies such as multiple myeloma, waldenström's macroglobulinemia, and certain forms of amyloidosis. abnormal b cells may be relatively large and some diseases include this in their names, such as diffuse large b-cell lymphomas (dlbcls) and intravascular large b-cell lymphoma. patients with b cell alymphocytosis are predisposed to infections. epigenetics a study that investigated the methylome of b cells along their differentiation cycle, using whole-genome bisulfite sequencing (wgbs), showed that there is a hypomethylation from the earliest stages to the most differentiated stages. the largest methylation difference is between the stages of germinal center b cells and memory b cells. furthermore, this study showed that there is a similarity between b cell tumors and long-lived b cells in their dna methylation signatures.