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J. Exp. Med.,
Volume 186, Number 9, November 3, 1997 1547-1556
By
From the Division of Molecular Oncology, Department of Pathology, Brigham and Women's Hospital,
Harvard Medical School, Boston, Massachusetts 02115
B cells that mediate normal, T cell-dependent, humoral immune responses must first pass
through germinal centers (GCs) within the cortex of antigenically stimulated lymph nodes. As
they move through the dark zone and then the light zone in the GC, B cells are subjected to
somatic hypermutation and switch recombination within their rearranged immunoglobulin
genes and also participate in a number of other processes that control development into memory cells or cells specialized for antibody secretion. To investigate the molecular mechanisms
that contribute to B cell development within GCs, we constructed a recombinant DNA library
enriched for cDNAs derived from human genes expressed in B cells at this site. This library was
found to contain a cDNA structurally and functionally related to genes in bacteria and yeast for
the DNA repair enzyme 8-oxoguanine DNA glycosylase. Northern blot analysis indicated that
the human gene is expressed as two alternatively spliced messenger RNAs within GC B cells at
levels greatly exceeding that found in other tissues. In situ hybridization studies revealed that
expression of this gene is most abundant within the dark zones of GCs. Both the function and
localized expression of this gene suggest that it may play a role in somatic hypermutation of immunoglobulin genes.
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