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


Autoria(s): Duchez S.; Amin R.; Cogné N.; Delpy L.; Sirac C.; Pascal V.; Corthésy B.; Cogné M.
Data(s)

2010

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_9E0C8E29D580

isbn:1091-6490[electronic], 0027-8424[linking]

pmid:20133609

doi:10.1073/pnas.0912393107

isiid:000274599500065

Idioma(s)

en

Fonte

Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 7, pp. 3064-3069

Palavras-Chave #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
Tipo

info:eu-repo/semantics/article

article