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PMID: 8376935 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells.

The Journal of experimental medicine ·Vol. 178 ·No. 4 ·1993-10-01 ·Pages 1293-307

Jacob J, Przylepa J, Miller C, Kelsoe G

Abstract

In the murine spleen, germinal centers are the anatomic sites for antigen-driven hypermutation and selection of immunoglobulin (Ig) genes. To detail the kinetics of Ig mutation and selection, 178 VDJ sequences from 16 antigen-induced germinal centers were analyzed. Although germinal centers appeared by day 4, mutation was not observed in germinal center B cells until day 8 postimmunization; thereafter, point mutations favoring asymmetrical transversions accumulated until day 14. During this period, strong phenotypic selection on the mutant B lymphocytes was inferred from progressively biased distributions of mutations within the Ig variable region, the loss of crippling mutations, decreased relative clonal diversity, and increasingly restricted use of canonical gene segments. The period of most intense selection on germinal center B cell populations preceded significant levels of mutation and may represent a physiologically determined restriction on B cells permitted to enter the memory pathway. Noncanonical Ig genes recovered from germinal centers were mostly unmutated although they probably came from antigen-reactive cells. Together, these observations demonstrate that the germinal center microenvironment is rich and temporally complex but may not be constitutive for somatic hypermutation.

MeSH Terms
Animals B-Lymphocytes/cytology,immunology Base Sequence DNA, Single-Stranded Female Genes, Immunoglobulin Immunoglobulin Heavy Chains/genetics,immunology Immunoglobulin Variable Region/genetics,immunology Kinetics Mice Mice, Inbred C57BL Molecular Sequence Data Mutation Nitrophenols/immunology Phenotype Phenylacetates Polymerase Chain Reaction Spleen/cytology,immunology
Chemicals
DNA, Single-Stranded Immunoglobulin Heavy Chains Immunoglobulin Variable Region Nitrophenols Phenylacetates 4-hydroxy-5-nitrophenyl acetic acid
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Jacob J
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore 21201.
Przylepa J
Miller C
Kelsoe G
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.178.4.1293
Published
1993-10-01
Pages
1293-307
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191212
Subset
IM
Grants
NIA NIH HHS · AG-08182 · United States
NIAID NIH HHS · AI-24335 · United States
Databases
GENBANK
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External Links
PubMed source DOI: 10.1084/jem.178.4.1293 PMC Full Text View journal details
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