The microenvironmental organization of early B cell precursors in the femoral bone marrow of mutant SCID mice, SCOD/myc transgenic mice and alternate fraction x-irradiated endocolonized mice /

The in situ microenvironmental organization of early precursor B cells in mouse bone marrow has been studied using three experimental models: (1) mutant mice with severe combined immunodeficiency (SCID), which develop pro-B cells but no pre-B and B cells; (2) SCID/myc transgenic mice having expanded pro-B cell populations, but no pre-B and B cells; (3) x-irradiated C3H/HeJ mice during early stages in the regeneration of pro-B cells in bone marrow seeded from a shielded marrow site. The in vivo localization of B220$ sp+$ cells was revealed by the binding of i.v. injected $ sp{125}$I-mAb 14.8 detected by light and electron microscope radioautography of femoral marrow sections. Many B220$ sp+$ pro-B cells were located in peripheral regions of SCID and SCID/myc bone marrow, often in clusters, associated with an electron dense extracellular matrix and with the processes of stromal reticular cells. Many B220$ sp+$ cells were associated with macrophages which contained numerous ingested bodies. Macrophage associations were more numerous in SCID/myc than in SCID mice, especially in the peripheral marrow regions. 3-5 day post-irradiation endocolonizing marrow contained increasing numbers of B220$ sp+$ cells in subosteal and peripheral regions, situated both within sinusoids and extravascularly, associated with stromal reticular cell processes and often close to nerve fibers. The results demonstrate that early B220$ sp+$ precursors begin to differentiate in peripheral marrow regions and develop intimate associations with reticular cells and macrophages. These findings suggest that through these associations, the bone marrow reticular cells promote the early development of the B cell lineage, while the bone marrow macrophages play a role in the elimination of aberrant precursor B cells