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.
Laboratoire d'Immunologie, Université de Limoges, Centre National de la Recherche Scientifique Unité Mixte 6101, F-87025 Limoges, France.
Sophie
S
Duchez
Rada
R
Amin
Nadine
N
Cogné
Laurent
L
Delpy
Christophe
C
Sirac
Virginie
V
Pascal
Blaise
B
Corthésy
Michel
M
Cogné
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