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* Integrated Department of Immunology, University of Colorado Health Science Center and National Jewish Medical and Research Center, and
Division of Clinical Immunology, Department of Medicine, University of Colorado Health Science Center, Denver, CO 80206
Aging is accompanied by greatly reduced B cell production in the
bone marrow, yet peripheral B cell numbers do not decline. We
hypothesize that this may reflect filling of the peripheral pool with B
cells that are long-lived as a consequence of specificity for, and
chronic stimulation by, environmental Ags. To begin to explore this
possibility, we analyzed the effects of aging on B cell population
dynamics in the anti-H2k/b 3-83µ
Ig-transgenic
mouse. We predicted that, because they presumably do not bind
environmental Ags, B cells bearing the transgenic receptor may be lost
in aged animals. As seen in nontransgenic animals, total splenic B cell
numbers remained constant with age in the Ig-transgenic animals despite
reduced B cell production. Importantly, although the few newly produced
B cells in the bone marrow of aged mice are 3-83 positive, the
peripheral compartment of these mice is dominated by B cells that
express endogenous Ig genes rather than the transgenes. This population
includes large numbers of marginal zone-like and
CD21low/-CD23low/-IgMlow B cells,
as well as elevated numbers of CD5+ B cells. Many of these
cells express only non-B220 CD45 isoforms, suggesting that they may be
memory cells. A significant proportion of aged transgenic animals
produce autoantibodies that are reactive with ssDNA, dsDNA, or
histones. Results support the hypothesis that, in the face of severely
reduced production with age, B cells are selected based on reactivity
to environmental Ags, accumulate, and display activated phenotypes.
Cells bearing 3-83-transgenic receptors are excluded from this
population due to their specificity. Beyond their importance in aging,
these findings define a novel form of receptor revision in which B
cells are selected rather than deleted based on Ag
reactivity.
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