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Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702
The young rabbit appendix and the chicken bursa of Fabricius are
primary lymphoid organs where the B cell Ab repertoire develops in
germinal centers (GCs) mainly by a gene conversion-like process. In
human and mouse, V-gene diversification by somatic hypermutation in GCs
of secondary lymphoid organs leads to affinity maturation. We asked
whether gene conversion, somatic hypermutation, or both occur in rabbit
splenic GCs during responses to the hapten DNP. We determined DNA
sequences of rearranged heavy and light chain V region gene
segments in single cells from developing DNP-specific GCs after
immunization with DNP-bovine
-globulin and conclude that the changes
at the DNA level that may lead to affinity maturation occur by both
gene conversion and hypermutation. Selection was suggested by finding
some recurrent amino acid replacements that may contribute increased
affinity for antigen in the complementarity-determining region
sequences of independently evolved clones, and a narrower range of
complementarity-determining region 3 lengths at day 15. Some of the
alterations of sequence may also lead to new members of the B cell
repertoire in adult rabbits comparable with those produced in gut
associated lymphoid tissues of young rabbits.
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