We have previously shown that CO21high IgMhigh mouse B cells enriched in the marginal zone (MZ) are unique in both phenotype and function compared to CD21int. IgMint. follicular (FO) B cells. In the VH81x transgenic mouse, a predominant heavy and light chain pair gives rise to a prevailing idiotype (Id) which is expressed in the majority of B cells in the MZ. These Id+ B cells function similarly to MZ B cells found in other normal mouse strains. Since Id+ B cells bind phosphorylcholine (PC), we investigated the response to a T-independent antigen from a heat killed Strep. pneumoniae vaccine in these transgenic mice. 24 hours following i.v. injection of the vaccine, syndecanhigh, cytoplasmic μhigh, CD38low, B220low plasma cells were observed in the red pulp and this response peaked at 3 days. These plasma cells were derived from MZ B cells as shown by expression of the predominant Id found in the VH81x MZ B cell population. Furthermore, the MZ B cells incorporated more BrdU than FO B cells 3 days after immunization, indicating that these cells were undergoing more rapid cellular division. Finally, serum Ig levels indicated that Id+ Ig was secreted following immunization. Thus MZ B cells are able to quickly respond to T-independent antigens by differentiating into plasma cells and secreting antigen specific Ig.