Depletion of the predominant B-cell population in immunoglobulin mu heavy-chain transgenic mice.
The transgenic mouse line M54 was generated by introducing a functionally-rearranged immunoglobulin mu heavy-chain gene into the germ line of a C57B1/6 inbred mouse. Previous examination of the antibodies produced by B-cell hybridomas derived from transgenic M54 mice showed that the presence of the mu transgene grossly altered the immunoglobulin repertoire of unimmunized animals, suggesting that these mice suffer from a serious immunoregulatory perturbation. Studies presented here introduce a new perspective on this functional defect. We show that the lymphoid tissues from these transgenic mice lack virtually all conventional bone-marrow-derived B cells, which constitute the predominant B-cell population in normal mice and which typically produce primary and secondary antibody responses to T-cell-dependent antigens. Moreover, the bone marrow from transgenic M54 mice is depleted of pre-B lymphocytes, indicating a serious defect in early B-cell lymphopoiesis. In contrast, CD5 (Ly-1) B cells, a second B-cell population displaying a characteristic set of cell surface markers which are derived from distinct precursors in the peritoneum, are represented at normal frequencies in these transgenic mice. Thus, the presence of the rearranged immunoglobulin heavy-chain transgene in M54 mice results in an unexpected selective developmental defect that impairs the development of bone-marrow-derived pre-B and B cells without affecting Ly-1 B cells.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D005818:Genetic Engineering; D007072:Immunoglobulin D / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009030:Mosaicism
D007072:Immunoglobulin D; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains