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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.

Publication ,  Journal Article
Jacob, J; Przylepa, J; Miller, C; Kelsoe, G
Published in: J Exp Med
October 1, 1993

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.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

October 1, 1993

Volume

178

Issue

4

Start / End Page

1293 / 1307

Location

United States

Related Subject Headings

  • Spleen
  • Polymerase Chain Reaction
  • Phenylacetates
  • Phenotype
  • Nitrophenols
  • Mutation
  • Molecular Sequence Data
  • Mice, Inbred C57BL
  • Mice
  • Kinetics
 

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Jacob, J., Przylepa, J., Miller, C., & Kelsoe, G. (1993). 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. J Exp Med, 178(4), 1293–1307. https://doi.org/10.1084/jem.178.4.1293
Jacob, J., J. Przylepa, C. Miller, and G. Kelsoe. “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.J Exp Med 178, no. 4 (October 1, 1993): 1293–1307. https://doi.org/10.1084/jem.178.4.1293.
Jacob, J., et al. “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.J Exp Med, vol. 178, no. 4, Oct. 1993, pp. 1293–307. Pubmed, doi:10.1084/jem.178.4.1293.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

October 1, 1993

Volume

178

Issue

4

Start / End Page

1293 / 1307

Location

United States

Related Subject Headings

  • Spleen
  • Polymerase Chain Reaction
  • Phenylacetates
  • Phenotype
  • Nitrophenols
  • Mutation
  • Molecular Sequence Data
  • Mice, Inbred C57BL
  • Mice
  • Kinetics