PMID- 10430628
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20191023
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 190
IP  - 3
DP  - 1999 Aug 2
TI  - Relaxed negative selection in germinal centers and impaired affinity maturation
      in bcl-xL transgenic mice.
PG  - 399-410
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-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.
FAU - Takahashi, Y
AU  - Takahashi Y
AD  - Department of Microbiology and Immunology, University of Maryland School of
      Medicine, Baltimore 21201, USA.
FAU - Cerasoli, D M
AU  - Cerasoli DM
FAU - Dal Porto, J M
AU  - Dal Porto JM
FAU - Shimoda, M
AU  - Shimoda M
FAU - Freund, R
AU  - Freund R
FAU - Fang, W
AU  - Fang W
FAU - Telander, D G
AU  - Telander DG
FAU - Malvey, E N
AU  - Malvey EN
FAU - Mueller, D L
AU  - Mueller DL
FAU - Behrens, T W
AU  - Behrens TW
FAU - Kelsoe, G
AU  - Kelsoe G
LA  - eng
SI  - GENBANK/AF065343
SI  - GENBANK/AF065344
SI  - GENBANK/AF065345
SI  - GENBANK/AF065346
SI  - GENBANK/AF065347
SI  - GENBANK/AF065348
SI  - GENBANK/AF065349
SI  - GENBANK/AF065350
SI  - GENBANK/AF065351
SI  - GENBANK/AF065352
SI  - GENBANK/AF065353
SI  - GENBANK/AF065354
SI  - GENBANK/AF065355
SI  - GENBANK/AF065356
SI  - GENBANK/AF065357
SI  - GENBANK/AF065358
SI  - GENBANK/AF065359
SI  - GENBANK/AF065360
SI  - GENBANK/AF065361
SI  - GENBANK/AF065362
SI  - GENBANK/AF065363
SI  - GENBANK/AF065364
SI  - GENBANK/AF065365
SI  - GENBANK/AF065366
SI  - GENBANK/AF065367
SI  - GENBANK/AF065368
SI  - GENBANK/AF065369
SI  - GENBANK/AF065370
SI  - GENBANK/AF065371
SI  - GENBANK/AF065372
SI  - etc.
GR  - AG10207/AG/NIA NIH HHS/United States
GR  - AG13789/AG/NIA NIH HHS/United States
GR  - AI24335/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Antibodies)
RN  - 0 (Bcl2l1 protein, mouse)
RN  - 0 (Immunoglobulin Variable Region)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-X Protein)
SB  - IM
MH  - Animals
MH  - Antibodies/blood
MH  - Antibody Affinity/*genetics
MH  - Antibody Formation/genetics
MH  - Antibody-Producing Cells/cytology/immunology/metabolism/pathology
MH  - Apoptosis/*genetics/*immunology
MH  - B-Lymphocyte Subsets/cytology/immunology/metabolism/pathology
MH  - Bone Marrow Cells/immunology/pathology
MH  - Cell Differentiation/genetics/immunology
MH  - Cell Survival/genetics/immunology
MH  - Cells, Cultured
MH  - Gene Rearrangement, B-Lymphocyte, Heavy Chain/genetics
MH  - Germinal Center/*cytology/*immunology
MH  - Immunoglobulin Variable Region/genetics
MH  - Lymphocyte Count
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis/*genetics/immunology
MH  - Spleen
MH  - Transgenes/immunology
MH  - bcl-X Protein
PMC - PMC2195593
EDAT- 1999/08/03 00:00
MHDA- 1999/08/03 00:01
CRDT- 1999/08/03 00:00
PHST- 1999/08/03 00:00 [pubmed]
PHST- 1999/08/03 00:01 [medline]
PHST- 1999/08/03 00:00 [entrez]
AID - 10.1084/jem.190.3.399 [doi]
PST - ppublish
SO  - J Exp Med. 1999 Aug 2;190(3):399-410. doi: 10.1084/jem.190.3.399.