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

85 Citations (Scopus)

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

Fingerprint

Germinal Center
Transgenic Mice
Antibodies
Apoptosis
B-Lymphocytes
Transgenes
Serum
Genetically Modified Animals
Immunoglobulins
Immunization
Bone Marrow
Maintenance

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-x(L) transgenic mice. / Takahashi, Yoshimasa; Cerasoli, Douglas M.; Dal Porto, Joseph M.; Shimoda, Michiko; Freund, Robert; Fang, Wei; Telander, David G.; Malvey, Erika Nell; Mueller, Daniel L.; Behrens, Timothy W.; Kelsoe, Garnett.

In: Journal of Experimental Medicine, Vol. 190, No. 3, 02.08.1999, p. 399-409.

Research output: Contribution to journalArticle

Takahashi, Y, Cerasoli, DM, Dal Porto, JM, Shimoda, M, Freund, R, Fang, W, Telander, DG, Malvey, EN, Mueller, DL, Behrens, TW & Kelsoe, G 1999, 'Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-x(L) transgenic mice', Journal of Experimental Medicine, vol. 190, no. 3, pp. 399-409. https://doi.org/10.1084/jem.190.3.399
Takahashi, Yoshimasa ; Cerasoli, Douglas M. ; Dal Porto, Joseph M. ; Shimoda, Michiko ; Freund, Robert ; Fang, Wei ; Telander, David G. ; Malvey, Erika Nell ; Mueller, Daniel L. ; Behrens, Timothy W. ; Kelsoe, Garnett. / Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-x(L) transgenic mice. In: Journal of Experimental Medicine. 1999 ; Vol. 190, No. 3. pp. 399-409.
@article{0b3d4e33d4aa42b4a6919ba6926d0a09,
title = "Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-x(L) transgenic mice",
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.",
keywords = "Affinity maturation, Apoptosis, Bcl-x(L), Clonal selection, Germinal center",
author = "Yoshimasa Takahashi and Cerasoli, {Douglas M.} and {Dal Porto}, {Joseph M.} and Michiko Shimoda and Robert Freund and Wei Fang and Telander, {David G.} and Malvey, {Erika Nell} and Mueller, {Daniel L.} and Behrens, {Timothy W.} and Garnett Kelsoe",
year = "1999",
month = "8",
day = "2",
doi = "10.1084/jem.190.3.399",
language = "English (US)",
volume = "190",
pages = "399--409",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",

}

TY - JOUR

T1 - Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-x(L) transgenic mice

AU - Takahashi, Yoshimasa

AU - Cerasoli, Douglas M.

AU - Dal Porto, Joseph M.

AU - Shimoda, Michiko

AU - Freund, Robert

AU - Fang, Wei

AU - Telander, David G.

AU - Malvey, Erika Nell

AU - Mueller, Daniel L.

AU - Behrens, Timothy W.

AU - Kelsoe, Garnett

PY - 1999/8/2

Y1 - 1999/8/2

N2 - 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.

AB - 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.

KW - Affinity maturation

KW - Apoptosis

KW - Bcl-x(L)

KW - Clonal selection

KW - Germinal center

UR - http://www.scopus.com/inward/record.url?scp=0033517153&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033517153&partnerID=8YFLogxK

U2 - 10.1084/jem.190.3.399

DO - 10.1084/jem.190.3.399

M3 - Article

C2 - 10430628

AN - SCOPUS:0033517153

VL - 190

SP - 399

EP - 409

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 3

ER -