Premature replacement of mu with alpha immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation.

Details

Serval ID
serval:BIB_9E0C8E29D580
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Premature replacement of mu with alpha immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Duchez S., Amin R., Cogné N., Delpy L., Sirac C., Pascal V., Corthésy B., Cogné M.
ISSN
1091-6490[electronic], 0027-8424[linking]
Publication state
Published
Issued date
2010
Volume
107
Number
7
Pages
3064-3069
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Sequentially along B cell differentiation, the different classes of membrane Ig heavy chains associate with the Ig alpha/Ig beta heterodimer within the B cell receptor (BCR). Whether each Ig class conveys specific signals adapted to the corresponding differentiation stage remains debated. We investigated the impact of the forced expression of an IgA-class receptor throughout murine B cell differentiation by knocking in the human C alpha Ig gene in place of the S mu region. Despite expression of a functional BCR, homozygous mutant mice showed a partial developmental blockade at the pro-B/pre-BI and large pre-BII cell stages, with decreased numbers of small pre-BII cells. Beyond this stage, peripheral B cell compartments of reduced size developed and allowed specific antibody responses, whereas mature cells showed constitutive activation and a strong commitment to plasma cell differentiation. Secreted IgA correctly assembled into polymers, associated with the murine J chain, and was transported into secretions. In heterozygous mutants, cells expressing the IgA allele competed poorly with those expressing IgM from the wild-type allele and were almost undetectable among peripheral B lymphocytes, notably in gut-associated lymphoid tissues. Our data indicate that the IgM BCR is more efficient in driving early B cell education and in mucosal site targeting, whereas the IgA BCR appears particularly suited to promoting activation and differentiation of effector plasma cells.
Keywords
Animals, B-Lymphocytes/cytology, B-Lymphocytes/immunology, Bromodeoxyuridine, Flow Cytometry, Gene Targeting, Humans, Immunoglobulin alpha-Chains/immunology, Immunoglobulin alpha-Chains/metabolism, Immunoglobulin mu-Chains/immunology, Immunoglobulin mu-Chains/metabolism, Immunohistochemistry, Lymphopoiesis/immunology, Mice, Mice, Transgenic, Plasma Cells/cytology, Plasma Cells/immunology, Receptors, Antigen, B-Cell/metabolism, Reverse Transcriptase Polymerase Chain Reaction
Pubmed
Web of science
Open Access
Yes
Create date
09/03/2010 11:43
Last modification date
20/08/2019 15:04
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