Alteration of the B cell surface phenotype, immune response to phosphocholine and the B cell repertoire in M167 mu plus kappa transgenic mice.
M167, mu plus kappa, transgenic mice have been analyzed for the expression of the transgene product as a cell surface, Ag-specific receptor and for their ability to respond to Ag. The vast majority of B cells in these H + L transgenics (97 to 99%) express large amounts of the transgene product on their surface and are capable of binding phosphocholine. A total of 4 to 30% of the B cells also express endogenous IgM and IgD H chain products. After immunization with phosphocholine (PC)-conjugated keyhole limpet hemocyanin, more than 1000 micrograms/ml of anti-PC antibody bearing the transgene IgMa allotype marker are produced. Surprisingly, significant amounts of anti-PC antibodies that express the endogenous, IgMb allotype, are also produced; however, these antibodies lack the T15-idiotype which dominates the anti-PC response in their nontransgenic littermate controls. The B cells producing these endogenous anti-PC antibodies also fail to switch to IgG anti-PC synthesis, whereas B cells producing anti-keyhole limpet hemocyanin antibodies readily undergo class switching. These last two observations may be due to the fact that the endogenous anti-PC antibody actually results from mixed mu a + mu b molecules in which the transgene encoded H and L chains are most likely responsible for the binding of PC. Thus, a switch of the endogenous isotype from mu b to IgG would result in a loss of specificity for PC in the IgG molecules produced using the endogenous VH-gene product(s), and mu a + gamma b hybrid molecules are not likely to be formed. This hypothesis is supported by the fact that the majority of (mu a + mu b) hybridomas have the mu b-allotype joined with a VH region other than the VH1 gene which is required for PC-binding and T15 idiotype expression.
Kenny
J J
JJ
Program Resources Inc., NCI-FCRF, Frederick, MD 21701.
Finkelman
F
F
Macchiarini
F
F
Kopp
W C
WC
Storb
U
U
Longo
D L
DL
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D001402:B-Lymphocytes / Q000145:classification* / Q000276:immunology / Q000378:metabolism; D002794:Choline / Q000031:analogs & derivatives*; D003433:Crosses, Genetic; D005260:Female; D005434:Flow Cytometry; D006433:Hemocyanins / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D010767:Phosphorylcholine / Q000276:immunology*; D013154:Spleen
D000954:Antigens, Surface; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D010767:Phosphorylcholine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D002794:Choline