Strain-specific silencing of a predominant antidextran clonotype family.
The immune response to dextran is characterized by marked phenotypic differences among murine strains. In particular, Igha strains, as opposed to strains of other Igh haplotypes, respond relatively vigorously to dextran B1355 fraction S (DEX), producing predominantly antibodies bearing the lambda light chain, and specific for the alpha(1----3) glucose linkage. We have investigated this disparity in BALB/c (Igha) vs. C.B20 (Ighb) mice at the individual precursor cell level. Consistent with previous findings (7-9, 35, 40, 42, 43), there was a 10-fold higher frequency of lambda-bearing splenic B cells specific for the alpha(1----3) linkage in Igha mice. As with previously studied (25-27) predominant specificities, the origin of this high frequency of lambda-bearing alpha(1----3) DEX-specific B cells appears to be a reflection of a high expression of this specificity in surface Ig (sIg)-negative cells emerging from the bone marrow generative cell pool. Surprisingly, although C.B20 mice (Ighb) have a low frequency of lambda-bearing alpha(1----3) DEX-specific B cells in their mature primary splenic population, the frequency of precursor cells of this clonotype in their sIg- bone marrow cell population is equivalent to that of BALB/c sIg- cells. These cells could only be stimulated in allotype allogeneic (Igha), as opposed to allotype syngeneic (Ighb), carrier-primed irradiated recipients. This finding was confirmed by the finding that a high proportion of antidextran hybridoma cell lines derived from C.B20 bone marrow cells produced lambda-bearing alpha(1----3) DEX-specific antibodies that were IdX+. These findings have led us to conclude that the well-established phenotypic difference between Igha and Ighb mice with respect to the expression of lambda-bearing alpha(1----3) DEX-specific antibody responses is not, as previously assumed, the result of an inability of Ighb mice to generate B cells of this clonotype, but rather, is the product of environmental, possibly antiidiotypic, silencing of cells of this clonotype as they mature in Ighb mice.
B G
BG
Froscher
N R
NR
Klinman
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D003911:Dextrans / Q000276:immunology*; D008040:Genetic Linkage; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008815:Mice, Inbred Strains / Q000276:immunology*; D013045:Species Specificity; D013154:Spleen / Q000276:immunology
D003911:Dextrans