B-less: a strain of profoundly B cell-deficient mice expressing a human lambda transgene.
We have created several transgenic mouse strains that bear the human lambda light chain gene driven by its own promoter and a mouse immunoglobulin heavy chain enhancer. The transgene is expressed in many tissues, with particularly high levels of expression in the bone marrow, thymus, spleen, and lymph nodes. One of these transgenic lines, B-less, displays a dramatic phenotype characterized by an acute susceptibility to bacterial and viral infections. Analysis of this strain shows it to be profoundly deficient in both immature (pre-B) and mature B cells, as well as in circulating immunoglobulin. The pre-B and B cell defects are cell autonomous, as judged by cell culture and bone marrow graft chimeras. Despite this B cell deficiency, the T cell lineage appears grossly normal as assessed by flow cytometric analysis and by its response to mitogen stimulation. Since an independently derived transgenic strain bearing the same human lambda construct displays a partial B-less phenotype, it is likely that the B lineage deficiency is due to a dominant effect of transgene expression rather than to the insertional perturbation of an endogenous mouse gene. It is interesting that the deficiency phenotype is fully expressed in the FVB/N genetic background, but is suppressed in F1 hybrids formed between the FVB/N and C57BL/6 inbred strains. Evidently, there are one or more dominant genetic suppressors of B-less in the C57BL/6 genome.
Vasicek
T J
TJ
Howard Hughes Medical Institute, Boston, Massachusetts.
Levinson
D A
DA
Schmidt
E V
EV
Campos-Torres
J
J
Leder
P
P
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D015139:Blotting, Southern; D002460:Cell Line; D002472:Cell Transformation, Viral; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007121:Immunocompetence; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D009052:Leukemia Virus, Murine; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype
D007146:Immunoglobulin lambda-Chains