Definition of a novel cellular constituent of the bone marrow that regulates the response of immature B cells to B cell antigen receptor engagement

Previously we defined a Thy1(dull) bone marrow-derived cell population that regulated fate decisions by immature B cells after Ag receptor signaling. The microenvironmental signals provided by this cell population were shown to redirect the B cell Ag receptor -induced apoptotic response of immature B cells toward continued recombination-activating gene (RAG) expression and secondary light chain recombination (receptor editing). Neither the identi ty of the cell responsible for this activity nor its role in immature B cel l development in vivo were addressed by these previous studies. Here we sho w that this protective microenvironmental niche is defined by the presence of a novel Thy1(dull), DX5(pos) cell that can be found in close association with immature B cells in vivo. Depletion of this cell eliminates the anti- apoptotic effect of bone marrow in vitro and leads to a significant decreas e in the number and frequency of bone marrow immature B cells in vivo. We p ropose that, just as the bone marrow environment is essential for the survi val and progression of pro-B and pre-B cells through their respective devel opmental checkpoints, this cellular niche regulates the progression of imma ture stage B cells through negative selection.