Inconclusive Evidence for or against Positive Antigen Selection in the Shaping of Human Immunoglobulin E Repertoires: A Call for New Approaches.
(2013) In International Archives of Allergy and Immunology 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:
https://lup.lub.lu.se/record/3412080
- author
- Levin, Mattias LU and Ohlin, Mats LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- International Archives of Allergy and Immunology
- volume
- 161
- issue
- 2
- pages
- 122 - 126
- publisher
- Karger
- external identifiers
-
- wos:000314995100004
- pmid:23343692
- scopus:84872816243
- pmid:23343692
- ISSN
- 1423-0097
- DOI
- 10.1159/000345421
- project
- Human IgE repertoires and an anti-allergome resource
- language
- English
- LU publication?
- yes
- id
- 5e07b75e-0e40-45f5-b92c-732e0ed4c39c (old id 3412080)
- date added to LUP
- 2016-04-04 08:55:18
- date last changed
- 2022-03-31 00:32:28
@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 Immunology}}, title = {{Inconclusive Evidence for or against Positive Antigen Selection in the Shaping of Human Immunoglobulin E Repertoires: A Call for New Approaches.}}, url = {{https://lup.lub.lu.se/search/files/5209994/3412084.pdf}}, doi = {{10.1159/000345421}}, volume = {{161}}, year = {{2013}}, }