PMID- 23343692
OWN - NLM
STAT- MEDLINE
DCOM- 20131018
LR  - 20141120
IS  - 1423-0097 (Electronic)
IS  - 1018-2438 (Linking)
VI  - 161
IP  - 2
DP  - 2013
TI  - Inconclusive evidence for or against positive antigen selection in the shaping of 
      human immunoglobulin E repertoires: a call for new approaches.
PG  - 122-6
LID - 10.1159/000345421 [doi]
AB  - BACKGROUND: The mechanisms driving the development of immunoglobulin E (IgE) 
      antibody repertoires are a matter of debate. Alternatives to the classical view 
      on antibody development, involving somatic mutation and antigen-driven selection 
      of high-affinity variants in germinal centers, have been proposed. METHODS: We 
      have re-analyzed the pattern of mutations in previously isolated and 
      characterized human clonally unrelated IgE-encoding transcripts using the 
      validated focused binomial methodology to find evidence in such genes of 
      antigen-specific selection. RESULTS: As expected there is a selection against 
      replacement mutations in IgE framework regions. In contrast, in all examined 
      cases but one (assessing IgE repertoires of parasite-infected individuals) there 
      was no evidence in favor of either positive or negative selection in 
      complementarity determining regions. Importantly, however, the validated method 
      also failed to detect selection for replacement mutations in two, non-IgE, 
      hypermutated antibody populations targeting tetanus toxoid and vaccinia virus, 
      respectively. CONCLUSIONS: Current methodology is unable to define with 
      certainty, using commonly assessed IgE repertoire sizes, whether antigen 
      selection is or is not a major driving force in the establishment of human IgE. 
      New approaches are needed to address this matter.
CI  - Copyright (c) 2013 S. Karger AG, Basel.
FAU - Levin, Mattias
AU  - Levin M
AD  - Department of Immunotechnology, Lund University, Lund, Sweden.
FAU - Ohlin, Mats
AU  - Ohlin M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130122
PL  - Switzerland
TA  - Int Arch Allergy Immunol
JT  - International archives of allergy and immunology
JID - 9211652
RN  - 0 (Codon)
RN  - 0 (Complementarity Determining Regions)
RN  - 0 (Epitopes)
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - 0 (Immunoglobulin Idiotypes)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Codon
MH  - Complementarity Determining Regions/genetics/immunology
MH  - Epitopes/genetics/immunology
MH  - Humans
MH  - Immunoglobulin E/*genetics/*immunology
MH  - Immunoglobulin Heavy Chains/genetics/immunology
MH  - Immunoglobulin Idiotypes/genetics/immunology
MH  - Leukocytes, Mononuclear/immunology
MH  - Models, Statistical
MH  - Mutation
MH  - Nasal Mucosa/*immunology
MH  - Rhinitis, Allergic
MH  - Rhinitis, Allergic, Perennial/genetics/*immunology
EDAT- 2013/01/25 06:00
MHDA- 2013/10/19 06:00
CRDT- 2013/01/25 06:00
PHST- 2012/08/07 00:00 [received]
PHST- 2012/10/24 00:00 [accepted]
PHST- 2013/01/25 06:00 [entrez]
PHST- 2013/01/25 06:00 [pubmed]
PHST- 2013/10/19 06:00 [medline]
AID - 000345421 [pii]
AID - 10.1159/000345421 [doi]
PST - ppublish
SO  - Int Arch Allergy Immunol. 2013;161(2):122-6. doi: 10.1159/000345421. Epub 2013 
      Jan 22.