Premature replacement of μ with α immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation

• DOI: 10.1073/pnas.0912393107
• Publication Date: 2010-01-29T03:53:09Z
• Authors: Sophie Duchez; Rada Amin; Nadine Cogné; Laurent Delpy; Christophe Sirac; Virginie Pascal; Blaise Corthésy; Michel Cogné
• Keywords: Lymphopoiesis; breakpoint cluster region; Immunoglobulin A; Allelic exclusion; Immunoglobulin heavy chain; J chain; PAX5

Sequentially along B cell differentiation, the different classes of membrane Ig heavy chains associate with Igα/Igβ heterodimer within receptor (BCR). Whether each class conveys specific signals adapted to corresponding differentiation stage remains debated. We investigated impact forced expression an IgA-class throughout murine by knocking in human Cα gene place Sμ region. Despite a functional BCR, homozygous mutant mice showed partial developmental blockade at pro-B/pre-BI and large pre-BII stages, decreased numbers small cells. Beyond this stage, peripheral compartments reduced size developed allowed antibody responses, whereas mature cells constitutive activation strong commitment plasma differentiation. Secreted IgA correctly assembled into polymers, associated J chain, was transported secretions. In heterozygous mutants, expressing allele competed poorly those IgM from wild-type were almost undetectable among lymphocytes, notably gut-associated lymphoid tissues. Our data indicate that BCR is more efficient driving early education mucosal site targeting, appears particularly suited promoting effector