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Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-xL transgenic mice.

Publication ,  Journal Article
Takahashi, Y; Cerasoli, DM; Dal Porto, JM; Shimoda, M; Freund, R; Fang, W; Telander, DG; Malvey, EN; Mueller, DL; Behrens, TW; Kelsoe, G
Published in: J Exp Med
August 2, 1999

The role of apoptosis in affinity maturation was investigated by determining the affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific antibody-forming cells (AFCs) and serum antibody in transgenic mice that overexpress a suppressor of apoptosis, Bcl-xL, in the B cell compartment. Although transgenic animals briefly expressed higher numbers of splenic AFCs after immunization, the bcl-xL transgene did not increase the number or size of germinal centers (GCs), alter the levels of serum antibody, or change the frequency of NP-specific, long-lived AFCs. Nonetheless, the bcl-xL transgene product, in addition to endogenous Bcl-xL, reduced apoptosis in GC B cells and resulted in the expansion of B lymphocytes bearing VDJ rearrangements that are usually rare in primary anti-NP responses. Long-lived AFCs bearing these noncanonical rearrangements were frequent in the bone marrow and secreted immunoglobulin G(1) antibodies with low affinity for NP. The abundance of noncanonical cells lowered the average affinity of long-lived AFCs and serum antibody, demonstrating that Bcl-xL and apoptosis influence clonal selection/maintenance for affinity maturation.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

August 2, 1999

Volume

190

Issue

3

Start / End Page

399 / 410

Location

United States

Related Subject Headings

  • bcl-X Protein
  • Transgenes
  • Spleen
  • Proto-Oncogene Proteins c-bcl-2
  • Molecular Sequence Data
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Count
  • Immunology
 

Citation

APA
Chicago
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MLA
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Takahashi, Y., Cerasoli, D. M., Dal Porto, J. M., Shimoda, M., Freund, R., Fang, W., … Kelsoe, G. (1999). Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-xL transgenic mice. J Exp Med, 190(3), 399–410. https://doi.org/10.1084/jem.190.3.399
Takahashi, Y., D. M. Cerasoli, J. M. Dal Porto, M. Shimoda, R. Freund, W. Fang, D. G. Telander, et al. “Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-xL transgenic mice.J Exp Med 190, no. 3 (August 2, 1999): 399–410. https://doi.org/10.1084/jem.190.3.399.
Takahashi Y, Cerasoli DM, Dal Porto JM, Shimoda M, Freund R, Fang W, et al. Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-xL transgenic mice. J Exp Med. 1999 Aug 2;190(3):399–410.
Takahashi, Y., et al. “Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-xL transgenic mice.J Exp Med, vol. 190, no. 3, Aug. 1999, pp. 399–410. Pubmed, doi:10.1084/jem.190.3.399.
Takahashi Y, Cerasoli DM, Dal Porto JM, Shimoda M, Freund R, Fang W, Telander DG, Malvey EN, Mueller DL, Behrens TW, Kelsoe G. Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-xL transgenic mice. J Exp Med. 1999 Aug 2;190(3):399–410.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

August 2, 1999

Volume

190

Issue

3

Start / End Page

399 / 410

Location

United States

Related Subject Headings

  • bcl-X Protein
  • Transgenes
  • Spleen
  • Proto-Oncogene Proteins c-bcl-2
  • Molecular Sequence Data
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Count
  • Immunology