Very low affinity B cells form germinal centers, become memory B cells, and participate in secondary immune responses when higher affinity competition is reduced

JM Dal Porto, AM Haberman, G Kelsoe… - The Journal of …, 2002 - rupress.org
The Journal of experimental medicine, 2002rupress.org
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) mice
were created. H50Gμa and T1 (V23) μa mice express μ H chain transgenes that associate
with the λ1 L chains to bind the (4-hydroxy-3-nitrophenyl) acetyl hapten with association
constants (K as) of only 1.2× 105 M− 1 and 3× 104 M− 1, respectively. Both lines mounted
substantial antibody-forming cell (AFC) and germinal center (GC) responses. H50Gμa Tg …
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) mice were created. H50Gμa and T1(V23)μa mice express μ H chain transgenes that associate with the λ1 L chains to bind the (4-hydroxy-3-nitrophenyl)acetyl hapten with association constants (Kas) of only 1.2 × 105 M−1 and 3 × 104 M−1, respectively. Both lines mounted substantial antibody-forming cell (AFC) and germinal center (GC) responses. H50Gμa Tg mice also generated memory B cells. T1(V23)μa 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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