Premature replacement of mu with alpha immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation.
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.
Duchez
Sophie
S
Laboratoire d'Immunologie, Université de Limoges, Centre National de la Recherche Scientifique Unité Mixte 6101, F-87025 Limoges, France.
Amin
Rada
R
Cogné
Nadine
N
Delpy
Laurent
L
Sirac
Christophe
C
Pascal
Virginie
V
Corthésy
Blaise
B
Cogné
Michel
M
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001973:Bromodeoxyuridine; D005434:Flow Cytometry; D018390:Gene Targeting; D006801:Humans; D007137:Immunoglobulin alpha-Chains / Q000276:immunology / Q000378:metabolism*; D007148:Immunoglobulin mu-Chains / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007137:Immunoglobulin alpha-Chains; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell; D001973:Bromodeoxyuridine