Effect of different Ig transgenes on B cell differentiation in scid mice.
In this study we show that the ability of bone marrow pre-B cells to differentiate into B cells in H/L chain transgenic scid mice correlates with the ability of the transgenes to inhibit initiation of endogenous kappa gene rearrangement. Initiation of rearrangement was scored by assaying for DNA double-strand breaks (DSB) at the recombination signal/coding borders of J kappa 1 and J kappa 2. In H/L chain transgenic scid mice that develop B cells, we found little or no DSB; whereas in H chain only transgenic scid mice, in which pre-B cells are unable to give rise to B cells, we found a normal level of DSB but no VJ kappa coding joints. As scid mice are deficient in the repair of DSB, we suggest that initiation of kappa gene rearrangement in H chain transgenic scid mice causes B lineage cells to die at the late pre-B stage. In one transgenic scid line (Y-Sp6), which falls to generate B cells despite containing a H and L chain transgene, we found evidence for loss of B lineage cells at two stages of development: the pro-B to pre-B transitional stage and the late pre-B stage.
Chang
Y
Y
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Bosma
M J
MJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation; D017637:Clonal Deletion; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D016511:Severe Combined Immunodeficiency / Q000276:immunology* / Q000473:pathology; D019076:Transgenes
D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains