Premature replacement of {micro} with {alpha} immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2010

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

Résumé

Sequentially along B cell differentiation, the different classes of membrane Ig heavy chains associate with the Igalpha/Igbeta 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 Calpha Ig gene in place of the Smu 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.

Domaines

Immunologie

Dates et versions

hal-00454129 , version 1 (08-02-2010)

Identifiants

Citer

Sophie Duchez, Rada Amin, Nadine Cogné, Laurent Delpy, Christophe Sirac, et al.. Premature replacement of {micro} with {alpha} immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation.. Proceedings of the National Academy of Sciences of the United States of America, 2010, epub ahead of print. ⟨10.1073/pnas.0912393107⟩. ⟨hal-00454129⟩
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