Plasmacytic differentiation of marginal zone and follicular B cells

It has previously been proposed that the rapid and robust activity MZB cells exhibit early during immune responses occurs because these cells are "pre-activated." I have further delineated this pre-activated phenotype as it relates to plasma cell differentiation.; First, I compared the inherent capacity of MZB and follicular B (FOB) cells, which represent the majority of mature splenic B lymphocytes, to respond to the T-I stimulus LPS in vitro. My results revealed that MZB cells express approximately three times more cell surface RP105/MD-1, a LPS-responsive Toll receptor, than do FOB cells. Furthermore, I determined that MZB cells induce IgM secretion in response to 100-fold lower LPS concentrations than do FOB cells. Thus, I conclude that MZB cells are specialized in detecting and responding to the TLR ligand LPS.; Next, I demonstrated that the rapid initiation of IgM secretion by MZB cells cannot be accounted for by enhanced basal expression of immunoglobulin components.; Upon LPS stimulation, the MZB and FOB cell populations both augment the secretory pathway. The extent of expansion correlates with the kinetics of antibody secretion, with MZB cells exhibiting a more rapid ER expansion. Most interestingly, in my in vitro studies using LPS stimulation, the rate of IgM secretion was greater by MZB cells than FOB cells at each timepoint assessed.; In summary, my research has demonstrated that MZB cells possess a unique molecular and ultrastructural profile, which I propose facilitates their rapid differentiation into antibody-secreting cells as front-line responders in humoral immunity. Importantly, the function and cell surface marker phenotype of human MZB cells are remarkably similar to that of murine MZB cells, suggesting that my findings may also pertain to human MZB cell function. The information gained from this work impacts the fields of immunology and B cell biology and provides a foundation for future studies of the small and intriguing MZB cell subpopulation. (Abstract shortened by UMI.)...