Newly formed B cells can go to the splenic follicular or marginal zone but the factors affecting this choice are not known. We have followed the in vivo generation and functional capabilities of a cohort of identical B cell (Id+) clones that is enriched in the CD21highIgHIGH marginal zone (MZ) B cell repertoire of the VH81X transgenic (tg) mouse. Although the number of Id+cells generated in the bone marrow of tg, tg CD40LT and tg xid mice is comparable, in only the first two these cells are enriched in the MZ. Tg xid mice are able to generate reduced numbers of MZ Id+ cells with phenotype and lifespan similar to normal MZ B cells, however these cells do not respond to an in vivo T independent (TI) antigenic stimulation by heat killed S. Pneumoniae vaccine. MZ B cells generated plasmablasts after challenge in both tg and tg CD40LT mice Id+ beginning at 24 hrs and peaking at 3-4 days while in the tg xid they did not. These data suggest that due to their btk-dependent signaling defect tg xid mice develop two malfunctions of the B cell compartment: first he inability to generate normal numbers of MZ Id+ effector cells and second the cells that are generated do not respond to the antigenic challenge.