Normal serum immunoglobulins participate in the selection of peripheral B-cell repertoires.
In B-cell development, expression of immunoglobulin heavy-chain variable-region (VH) gene repertoires is determined by genetic mechanisms that favor rearrangement of the most D-proximal genes, resulting in overutilization of the VH7183 gene family early in ontogeny and in differentiating B cells of the adult bone marrow. Maturation of the immune system is accompanied by a decreased expression of VH7183 genes in the peripheral immunocompetent B-cell pool of adult animals. By comparing VH gene family expression in the bone marrow (emergent) and peripheral (available and actual) B-cell repertoires of germ-free and conventionally raised BALB/c mice, we found that peripheral selection of VH gene family utilization does not occur in germ-free animals. Reconstitution of germ-free mice with normal serum immunoglobulins purified from syngeneic donors reestablishes selection of VH7183-expressing B cells. Our results indicate that preimmune B-cell repertoires are selected in normal animals by environmental antigens and serum immunoglobulins.
Freitas
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AA
Unité d'Immunobiologie, Institut Pasteur, Paris, France.
Viale
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Sundblad
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Heusser
C
C
Coutinho
A
A
D000818:Animals; D000916:Antibody Diversity; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells; D015342:DNA Probes; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D005856:Germ-Free Life; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007136:Immunoglobulins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009693:Nucleic Acid Hybridization; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology
D015342:DNA Probes; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins