Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 195, Issue 9, Pages 1215-1221Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20011550
Keywords
mutation; antibody affinity; plasma cell; variable region gene; lambda 1 immunoglobulin
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Funding
- NIAID NIH HHS [R01 AI024335, AI43603, R01 AI043603, AI24335, R56 AI043603] Funding Source: Medline
- NIA NIH HHS [AG13789, AG10207] Funding Source: Medline
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To understand the relationship between the affinity, of the B cell antigen receptor (BCR) and the immune response to antigen, two lines of immunoglobulin H chain transgenic (Tg) m-ice were created. H50Gmu(a) and T1(V23)mu(a) inice express mu H chain transgenes that associate with the lambda1 L chains to bind the (4-hydroxy-3-nitrophenyl)acetyl hapten with association constants (K(a)s) of only 1.2 X 10(5) M-1 and 3 X 10(4) M-1, respectively. Both lines mounted substantial antibody-forming cell (AFC) and germinal center (GC) responses. H50Gmu(a) Tg mice also generated memory B cells. T1(V23)mu(a) B cells formed AFC and GCs, but were largely replaced in late GCs by antigen-specific cells that express endogenous BCRs. Thus, B lymphocytes carrying BCRs with affinities previously thought to be irrelevant in specific immune responses are in fact capable of complete T cell-dependent immune responses when relieved of substantial competition from other B cells. The failure to observe such B cells normally in late primary responses and in memory B cell populations is the result of competition, rather than an intrinsic inability of low affinity B cells.
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