The Journal of Immunology, Vol 155, Issue 7 3377-3384, Copyright © 1995 by American Association of Immunologists

ARTICLES

Ig VH hypermutation is absent in the germinal centers of aged mice

C Miller and G Kelsoe
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore 21201, USA.

After injection with immunogenic conjugates of the hapten (4-hydroxy-3- nitrophenyl)acetyl (NP), two distinct B cell populations can be identified in the spleen during the primary response. One of these populations is specialized for Ab production; the other, the germinal centers (GCs), has been identified as the site of Ig somatic hypermutation. Ag-driven selection of GC B cells bearing mutated receptors with higher affinity leads to the affinity maturation of serum Ab and increased protective humoral immunity. Microdissection of GC B cell populations specific for NP and sequencing of the recovered Ig heavy chain variable region genes revealed that the somatic hypermutation process is absent in the GCs of aged C57BL/6 mice. However, selection for Ag appears to occur in the absence of hypermutation in the form of competition between unmutated clones of Ag- activated B lymphocytes. Thus, affinity maturation in these animals is limited to the affinities of Ab encoded by the germline.

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