TY - JOUR
T1 - Biased immunoglobulin variable region gene expression by Ly‐1 B cells due to clonal selection
AU - Pennell, Christopher A.
AU - Mercolino, Thomas J.
AU - Grdina, Therese A.
AU - Arnold, Larry W.
AU - Haughton, Geoffrey
AU - Clarke, Stephen H.
PY - 1989/7
Y1 - 1989/7
N2 - Most, if not all, autoantibodies specific for bromelain‐treated mouse erythrocytes recognize the common membrane phospholipid, phosphatidyl choline (PtC). Anti‐PtC antibodies are produced by 5%‐15% of CD5+ Ly‐1 B cells of normal unimmunized mice, but not by detectable numbers of conventional CD5– B cells. At 1 week of age PtC‐specific B cells are undetectable but then increase dramatically over the next 3 to 4 weeks to reach adult numbers. We report here that PtC‐specific Ly‐1 B cells in B10.H‐2aH‐4bp/Wts mice predominantly express either of two heavy and χ chain variable (V) region gene combinations. In addition, the sequence and length of DH genes are conserved among cells expressing the same V gene combination, and the Vχ‐Jχ junctions of one group involve unusual splice sites. Preferential V gene rearrangement models are insufficient to explain the DH and Vχ‐Jχ junctional sequences or the delayed appearance of this specificity, and so they cannot solely account for the high frequency of PtC‐specific cells. These characteristics are more consistent with antigen selection. We therefore attribute the frequent use of the two V region gene combinations to selection for cells that express them and conclude that the expressed V gene repertoire of Ly‐1 B cells in adult mice is influenced by antigen selection. Apparently, there is no selection for mutant anti‐PtC antibodies of higher affinity during the formation of the Ly‐1 B repertoire because the V region genes expressed by PtC‐specific cells are unmutated. Our findings are consistent with an important, germ line‐encoded function for the immunoglobulin products of these gene combinations.
AB - Most, if not all, autoantibodies specific for bromelain‐treated mouse erythrocytes recognize the common membrane phospholipid, phosphatidyl choline (PtC). Anti‐PtC antibodies are produced by 5%‐15% of CD5+ Ly‐1 B cells of normal unimmunized mice, but not by detectable numbers of conventional CD5– B cells. At 1 week of age PtC‐specific B cells are undetectable but then increase dramatically over the next 3 to 4 weeks to reach adult numbers. We report here that PtC‐specific Ly‐1 B cells in B10.H‐2aH‐4bp/Wts mice predominantly express either of two heavy and χ chain variable (V) region gene combinations. In addition, the sequence and length of DH genes are conserved among cells expressing the same V gene combination, and the Vχ‐Jχ junctions of one group involve unusual splice sites. Preferential V gene rearrangement models are insufficient to explain the DH and Vχ‐Jχ junctional sequences or the delayed appearance of this specificity, and so they cannot solely account for the high frequency of PtC‐specific cells. These characteristics are more consistent with antigen selection. We therefore attribute the frequent use of the two V region gene combinations to selection for cells that express them and conclude that the expressed V gene repertoire of Ly‐1 B cells in adult mice is influenced by antigen selection. Apparently, there is no selection for mutant anti‐PtC antibodies of higher affinity during the formation of the Ly‐1 B repertoire because the V region genes expressed by PtC‐specific cells are unmutated. Our findings are consistent with an important, germ line‐encoded function for the immunoglobulin products of these gene combinations.
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U2 - 10.1002/eji.1830190721
DO - 10.1002/eji.1830190721
M3 - Article
C2 - 2503389
AN - SCOPUS:0024318669
SN - 0014-2980
VL - 19
SP - 1289
EP - 1295
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 7
ER -