Regulation of cell survival during B lymphopoiesis: increased pre-B cell apoptosis in CD24-transgenic mouse bone marrow

Abstract

CD24 (heat‐stable antigen) is expressed in a developmentally regulated fashion by B cell precursors in mouse bone marrow (BM), but its role in B lymphopoiesis remains obscure. A slight overexpression of CD24 in transgenic (Tg) mice leads to depletion of B lymphoid cells in BM. The present study examines whether CD24 is involved in apoptotic selection of B lineage cells under normal microenvironmental conditions in vivo. Double immunofluorescence labeling and flow cytometry have been used to quantitate the apoptotic rates of phenotypically defined B cell populations in BM of CD24‐Tg mice. Apoptosis of pre‐B cells expressing cytoplasmic μ heavy chains of IgM but lacking surface (s)IgM was increased both ex vivo and in short‐term culture, while the number of pre‐B cells was halved compared to BM of normal mice. In contrast, B220+μ – pro‐B cells and sIgM+ B lymphocytes showed no significant change in either apoptosis or number. The findings provide evidence that CD24 can play a role in vivo in modulating pre‐B cell apoptosis, a quality control checkpoint in B cell development.

Bone Marrow B Cell Apoptosis During In Vivo Influenza Virus Infection Requires TNF-α and Lymphotoxin-α

“…It is currently unclear what other factors may influence the severity or duration of the BM B lineage cell depletion that occurs during influenza virus infection. IL-7, Abl protooncogene, limitin, CD24 expression, and hemopoietic growth factor cytokines such as fetal liver tyrosine kinase-ligand, can all influence the survival and proliferation of B lineage cells (51)(52)(53)(54), but any possible contribution by these or other factors to the phenomenon described in this study remains unknown. Moreover, cytokine-induced changes in the expression of intracellular anti-apoptotic factors would also be expected to contribute to sensitivity or resistance to TNF-␣ and LT␣-mediated apoptosis, but expression of these molecules has not yet been defined in this model.…”

Macrophage Depletion Suppresses Cardiac Allograft Vasculopathy in Mice

“…The severe reduction of vasculopathy observed with experimental transplants using the supposedly macrophage-deficient op/op osteopetrotic mice as recipients is also raised to implicate macrophages in CAV formation (26). The op/op mouse, however, also suffers from pleiotrophic immune defects such as aberrant granulocyte function, impaired Th1 differentiation and irregular B-cell lymphopoeisis (27)(28)(29). These confounding immune defects prevented the definitive interpretation of transplant experiments utilizing op/op mice, leaving the actual role of macrophages in CAV pathogenesis unresolved.…”

Mice Lacking Three Myeloid Colony-Stimulating Factors (G-CSF, GM-CSF, and M-CSF) Still Produce Macrophages and Granulocytes and Mount an Inflammatory Response in a Sterile Model of Peritonitis

“…Mice lacking RANK are characterized by profound osteopetrosis, a marked B cell deficiency, and enhanced extramedullary splenic hemopoiesis to compensate for an altered BM environment although it is not yet clear whether this is intrinsic to the hemopoietic cell lineage or whether the defect reflects alterations in the stromal environment (35). It is well-established that op/op mice are moderately lymphopenic (17); direct assessment of the B cell lineage has shown that B cell development is impaired and that there is increased apoptosis among precursor B cells (36). Close examination of B lymphopoiesis in marrow showed that the frequency of B cell progenitors (CFU-IL-7) is dramatically reduced, and interestingly, appears to be up-regulated in the liver but not the spleen (37).…”