Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-x(L) transgenic mice

Yoshimasa Takahashi, Douglas M. Cerasoli, Joseph M. Dal Porto, Michiko Shimoda, Robert Freund, Wei Fang, David G. Telander, Erika Nell Malvey, Daniel L. Mueller, Timothy W. Behrens, Garnett Kelsoe

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

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-x(L), in the B cell compartment. Although transgenic animals briefly expressed higher numbers of splenic AFCs after immunization, the bcl-x(L) 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-x(L) transgene product, in addition to endogenous bcl-x(L), 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 G1 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-x(L) and apoptosis influence clonal selection/maintenance for affinity maturation.

Original languageEnglish (US)
Pages (from-to)399-409
Number of pages11
JournalJournal of Experimental Medicine
Volume190
Issue number3
DOIs
StatePublished - Aug 2 1999
Externally publishedYes

Keywords

  • Affinity maturation
  • Apoptosis
  • Bcl-x(L)
  • Clonal selection
  • Germinal center

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Takahashi, Y., Cerasoli, D. M., Dal Porto, J. M., Shimoda, M., Freund, R., Fang, W., Telander, D. G., Malvey, E. N., Mueller, D. L., Behrens, T. W., & Kelsoe, G. (1999). Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-x(L) transgenic mice. Journal of Experimental Medicine, 190(3), 399-409. https://doi.org/10.1084/jem.190.3.399