lambda 5, but not mu, is required for B cell maturation in a unique gamma 2b transgenic mouse line.
gamma 2b transgenic mice have a severe B cell defect, apparently caused by strong feedback inhibition of endogenous H-gene rearrangement coupled with an inability of gamma 2b to provide the survival/maturation functions of mu. A unique gamma 2b transgenic line, named the C line, was found to permit B cell development. When the C line is crossed with a mu-membrane knockout line, gamma 2b+ B cells develop in the homozygous knockout. In contrast, a transgenic line representative of all the other gamma 2b lines is completely B cell deficient when mu-mem is deleted. Strikingly, the C phenotype is dominant in C x other gamma 2b transgenic line crosses. There is no evidence for higher gamma 2b transgene expression or other position effects on the transgene in the C mouse. The sequences of the three gamma 2b transgene copies in the C line are identical to that of the original transgene. These results have led to the conclusion that in the C line the transgene integration constitutively induces a gene whose expression can replace mu. To more clearly delineate the stage at which the altered phenotype of the C line is expressed, C mice were crossed onto a lambda 5 knockout background. In the absence of lambda 5, the C line produces no B cells. Since it was also found that gamma 2b can associate with the surrogate light chain (sL; lambda 5/Vpre-B), the crosses between C line gamma 2b mice and lambda 5 knockout mice suggest that gamma 2b/sL is required for B cell maturation in this mouse line. Thus, gamma 2b alone is unable to replace mu for pre-B cell survival/maturation; however, in combination with an unknown factor and the sL, gamma 2b can provide these nurturing functions.
Roth
P E
PE
Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637.
Kurtz
B
B
Lo
D
D
Storb
U
U
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D002874:Chromosome Mapping; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007142:Immunoglobulin gamma-Chains / Q000502:physiology*; D007146:Immunoglobulin lambda-Chains / Q000502:physiology*; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000502:physiology
D007075:Immunoglobulin M; D007142:Immunoglobulin gamma-Chains; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell