Inheritance of idiotype expression unlinked to the H chain allotype locus. Novel features of genetic control in the Ia.7 system.
We have observed a pattern of inherited idiotype expression in three mouse strains that is unexpected from the genetics of the strains: a dominant idiotype that was expressed at high levels in two parental strains was expressed only at low levels in a heavy chain allotype congenic strain derived from them. In the C3H.SW strain, the antibody response to the class II MHC Ag I-E is of limited diversity, with dominant expression of an idiotype and the V kappa 21 L chain. The C57BL/10 strain expresses the same idiotype at high levels, whereas the CWB/12 strain, which was derived by replacing the Ig H chain Igh-Cj allele of C3H.SW with the Igh-Cb allele derived from C57B1/10, has been found to express little of this dominant idiotype. CWB/12 responds, with titers equal to those of the parental strains, to the I-E epitope responsible for dominant idiotype expression, and it expresses normal V kappa 21 levels; thus deficiencies in epitope-specific responsiveness or in V kappa 21 expression cannot explain the low Id expression in CWB/12. Furthermore, Southern blot analysis of three VH families gave no evidence of recombination within the the VH locus of CWB/12, which was Igh-Vb throughout. Black-cross analysis demonstrated that expression of the dominant idiotype segregated independently of Ig allotype, and was therefore due to genes unlinked to the H chain gene locus. To our knowledge, this pattern of Id expression is unprecedented, and indicates the need for caution in the interpretation of studies using allotype congenic strains. It also demonstrates a role for genes outside the Igh locus in the control of Id expression.
Epstein
S L
SL
Molecular Immunology Laboratory, Food and Drug Administration, Bethesda, MD 20892.
Misplon
J A
JA
Arn
J S
JS
Max
E E
EE
Johnson-Leva
R
R
Harvath
L
L
Sachs
D H
DH
D000818:Animals; D003429:Cross Reactions; D003433:Crosses, Genetic; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D008040:Genetic Linkage; D005854:Germ Cells; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D007126:Immunoglobulin Allotypes / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007130:Immunoglobulin Idiotypes / Q000235:genetics* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007126:Immunoglobulin Allotypes; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region