PMID- 22903672
OWN - NLM
STAT- MEDLINE
DCOM- 20121001
LR  - 20161109
IS  - 0065-2598 (Print)
IS  - 0065-2598 (Linking)
VI  - 750
DP  - 2012
TI  - Control of B cells expressing naturally occurring autoantibodies.
PG  - 145-56
LID - 10.1007/978-1-4614-3461-0_11 [doi]
AB  - Naturally occurring autoantibodies (NAbs) are typically polyreactive, bind with 
      low affinity to a discrete set of autoantigens and are encoded by variable region 
      genes in germline configuration. They differ from disease-associated 
      autoantibodies (autoAb), which are mostly monoreactive, somatically mutated and 
      of high affinities. Structure-function studies have shown that polyreactivity of 
      NAbs relies on the somatically generated complementarity determining region, 
      CDR3, of the heavy chain. This finding suggested that NAb-producing B cells were 
      positively selected from the pre-immune B-cell repertoire. The biological 
      significance of this selection remains, however, unclear. Data originating mainly 
      from transgenic mice have shown that mature NAb-producing B cells are frequently 
      ignorant toward their antigen, possibly due to their low affinity, though active 
      tolerance mechanisms are not excluded. An important issue is whether 
      NAb-producing B cells constitute the pool from which pathologic auto Ab emerge 
      after autoantigen-driven maturation. We summarize results obtained in mouse 
      models, showing that some infectious agents are able to induce an 
      autoantigen-driven activation of certain NAb-producing B cells. However direct 
      proof that selection by autoantigen may lead to somatic hypermutation are still 
      lacking. Other data tend to suggest that pathologic auto Abs may derive from 
      non-autoimmune B cells that have diversified by somatic hypermutation of their 
      variable region genes.
FAU - Pasquali, Jean Louis
AU  - Pasquali JL
AD  - Clinical Immunology Department, National Referral Center for Systemic Autoimmune 
      Diseases, Nouvel Hopital Civil, Hopitaux Universitaires de Strasbourg, 
      Strasbourg, France.
FAU - Martin, Thierry
AU  - Martin T
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Adv Exp Med Biol
JT  - Advances in experimental medicine and biology
JID - 0121103
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Complementarity Determining Regions)
RN  - 0 (Immunoglobulin Variable Region)
SB  - IM
MH  - Animals
MH  - Antibody Affinity
MH  - Antibody Specificity
MH  - Autoantibodies/classification/*immunology
MH  - Autoantigens/immunology
MH  - *Autoimmunity
MH  - B-Lymphocytes/cytology/*immunology
MH  - Communicable Diseases/*immunology
MH  - Complementarity Determining Regions/immunology
MH  - Humans
MH  - Immunoglobulin Variable Region/genetics/immunology
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation
EDAT- 2012/08/21 06:00
MHDA- 2012/10/02 06:00
CRDT- 2012/08/21 06:00
PHST- 2012/08/21 06:00 [entrez]
PHST- 2012/08/21 06:00 [pubmed]
PHST- 2012/10/02 06:00 [medline]
AID - 10.1007/978-1-4614-3461-0_11 [doi]
PST - ppublish
SO  - Adv Exp Med Biol. 2012;750:145-56. doi: 10.1007/978-1-4614-3461-0_11.