Functional differences between marginal zone and follicular B cells in T-dependent immune responses

Mouse splenic B cells can be separated into 2 sub-populations based on the expression of cell surface antigens: marginal zone, CD23low CD21hi (MZ); and follicular, CD23hiCD21 int (FO) B-lymphocytes. Early involvement of MZ B cells in T-independent (TI) immune responses is well established. Upon in vitro activation, the expression of T cell co-stimulatory molecules are higher on MZ than on FO B cells, suggesting that MZ B cells provide early T cell co-stimulation. In this study, we have compared the abilities of MZ and FO B cells to perform the effector functions of antigen presentation, germinal center (GC) formation, and plasma-cell generation in response to T-dependent (TD) Ags. After immunization with soluble protein, both MZ and FO B cells capture Ag and migrate to T cell areas. However, due to high B7 expression on their cell surface, MZ B cells were more effective than FO B cells in inducing Ag-specific CD4+ T cell expansion both in vitro and in vivo. MZ B cells induced a rapid Ag-specific CD4+ T cell clonal expansion in vivo as early as day 2, and these MZ B cells subsequently differentiated into plasma cells detected at day 5 after cell transfer. In addition, MZ B cells stimulated Ag-specific CD4+ T cells to produce high level of Th1-like cytokines upon primary stimulation in vitro . In contrast. FO B cells participated actively in the GC formation and dominate in the later-appearing effector cells, including isotype-switched plasma cells, while MZ B cells developed rapidly into plasma cells in response to particulate Ag. These results indicate heterogeneity in the functions of mature splenic B cells. MZ B cells are more efficient than FO B cells in presenting Ag, leading to clonal expansion of Ag-specific CD4+ T cells. Interactions with T cells result in MZ B cells differentiating into plasma cells. On the other hand, FO B cells enter GC and may be the main source of memory B cells.