Stimulation by T cell independent antigens can relieve the arrest of differentiation of immature auto-reactive B cells in the bone marrow.
The pair of microH-chain and kappa L-chain transgenes encoding the Sp6 TNP/DNA-specific IgM was bred onto the rearrangement-deficient genetic background of RAG-2T mice, and onto the kappa L-chain expression-deficient background of iE kappa T mice. Bone marrow of Sp6 transgenic RAG-2T mice contained normal numbers of B220(CD45R)+c-kit+ pro/preB-I-like cells and normal numbers of B220(CD45R)+TAC+ preB-II-like cells. Most strikingly, the numbers of immature sIgM+ B cells in the bone marrow were at least five-fold lower than normal, while mature B cells were almost undetectable in bone marrow as well as spleen. Hence, B cell development in these mice appears to be arrested at the transition from preB-II to immature B cells. The contents of bone marrow and spleen of the different precursors, immature and mature B cell compartments in Sp6iE kappa T mice were found to be similar to those of normal mice except that all sIg+ cells expressed lambda L-chains, of which 40% coexpressed the transgenic kappa L-chain. It indicates that the repertoire of lambda L-chain rearrangements and the lambda L-chains expressed from it suffices to relieve the arrest of differentiation seen in Sp6RAG-2T mice. The T cell-independent antigen TNP-Ficoll elicited within 5 days a response of the Sp6RAG-2T mice to develop to IgM-secreting cells and to fill the serum pool with the Sp6 transgenic IgM to 100 micrograms/ml, i.e. to normal serum levels of IgM in normal mice. TNP-Ficoll appears to interfere with the arrest of differentiation. Two scenarios for this arrest of differentiation and its relief by the T-independent antigen TNP-Ficoll are discussed.
Andersson
J
J
Basel Institute for Immunology, Switzerland.
Melchers
F
F
Rolink
A
A
D000818:Animals; D000955:Antigens, T-Independent / Q000494:pharmacology*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005362:Ficoll / Q000031:analogs & derivatives / Q000494:pharmacology; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014301:Trinitrobenzenes / Q000494:pharmacology
D000955:Antigens, T-Independent; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; C020529:TNP-ficoll; D014301:Trinitrobenzenes; D005362:Ficoll