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Inconclusive Evidence for or against Positive Antigen Selection in the Shaping of Human Immunoglobulin E Repertoires: A Call for New Approaches.

Levin, Mattias LU and Ohlin, Mats LU (2013) In International Archives of Allergy and Immunology1994-01-01+01:00 161(2). p.122-126
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Archives of Allergy and Immunology1994-01-01+01:00
volume
161
issue
2
pages
122 - 126
publisher
Karger
external identifiers
  • wos:000314995100004
  • pmid:23343692
  • scopus:84872816243
ISSN
1423-0097
DOI
10.1159/000345421
language
English
LU publication?
yes
id
5e07b75e-0e40-45f5-b92c-732e0ed4c39c (old id 3412080)
date added to LUP
2013-01-29 12:57:41
date last changed
2019-03-08 02:57:57
@article{5e07b75e-0e40-45f5-b92c-732e0ed4c39c,
  abstract     = {The mechanisms driving the development of<br/><br>
immunoglobulin E (IgE) antibody repertoires are a matter of<br/><br>
debate. Alternatives to the classical view on antibody development,<br/><br>
involving somatic mutation and antigen-driven selection<br/><br>
of high-affinity variants in germinal centers, have<br/><br>
been proposed. Methods: We have re-analyzed the pattern<br/><br>
of mutations in previously isolated and characterized human<br/><br>
clonally unrelated IgE-encoding transcripts using the validated<br/><br>
focused binomial methodology to find evidence in<br/><br>
such genes of antigen-specific selection. Results: As expected<br/><br>
there is a selection against replacement mutations in IgE<br/><br>
framework regions. In contrast, in all examined cases but one<br/><br>
(assessing IgE repertoires of parasite-infected individuals)<br/><br>
there was no evidence in favor of either positive or negative<br/><br>
selection in complementarity determining regions. Importantly,<br/><br>
however, the validated method also failed to detect<br/><br>
selection for replacement mutations in two, non-IgE, hypermutated<br/><br>
antibody populations targeting tetanus toxoid and<br/><br>
vaccinia virus, respectively. Conclusions: Current methodology<br/><br>
is unable to define with certainty, using commonly assessed IgE repertoire sizes, whether antigen selection is or is<br/><br>
not a major driving force in the establishment of human IgE.<br/><br>
New approaches are needed to address this matter.},
  author       = {Levin, Mattias and Ohlin, Mats},
  issn         = {1423-0097},
  language     = {eng},
  number       = {2},
  pages        = {122--126},
  publisher    = {Karger},
  series       = {International Archives of Allergy and Immunology1994-01-01+01:00},
  title        = {Inconclusive Evidence for or against Positive Antigen Selection in the Shaping of Human Immunoglobulin E Repertoires: A Call for New Approaches.},
  url          = {http://dx.doi.org/10.1159/000345421},
  volume       = {161},
  year         = {2013},
}