Submitted May 2, 2006
Accepted November 13, 2006
Naive recirculating B cells mature simultaneously in the
spleen and bone marrow
Annaiah Cariappa, Catharine Chase, Haoyuan Liu, Paul Russell, and Shiv Pillai*
Massachusetts General Hospital, Harvard Medical School, Boston, MA
* Corresponding author; email: pillai{at}helix.mgh.harvard.edu.
We have recently demonstrated that IgDhi B cells can occupy an extravascular perisinusoidal niche in the bone marrow in addition to the well-established follicular niche in conventional secondary lymphoid organs. The spleen has long been considered to be the site at which newly formed B lymphocytes mature into IgDhi naive recirculating B cells, but the existence of mutant mice that have selectively lost mature B cells in the bone marrow prompted an examination of B cell maturation at this latter site. Following a single pulse of BrdU in intact mice, sequential labeling of more mature B cell populations in the bone marrow suggested ongoing maturation at this site. Further evidence for B cell maturation in the bone marrow was obtained from analyses of transitional B cells in splenectomized lymphotoxin alpha deficient mice that lack all secondary lymphoid organs. In these mice, antibody secreting cells recognizing multivalent antigens were also observed in the bone marrow following an intravenous microbial challenge. These data suggest that newly formed B cells mature into IgDhi B cells simultaneously in the spleen and the bone marrow, and establish in a stringent manner that humoral immune responses can be initiated in situ in the bone marrow.
