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Restricted IgA Repertoire in Both B-1 and B-2 Cell-Derived Gut Plasmablasts¹

Maaike Stoel^*,, Han-Qing Jiang, Cleo C. van Diemen^*, Judy C. A. M. Bun^*, Peter M. Dammers^*, M. Christine Thurnheer, Frans G. M. Kroese^*, John J. Cebra and Nicolaas A. Bos^2,*

^* Department of Cell Biology, Section Histology and Immunology, University of Groningen, Faculty Medical Sciences, Groningen, The Netherlands; and Department of Biology, University of Pennsylvania, Philadelphia, PA 19104

Mucosal IgA is the most abundantly produced Ig upon colonization of the intestinal tract with commensal organisms in the majority of mammals. The repertoire of these IgA molecules is still largely unknown; a large amount of the mucosal IgA cannot be shown to react with the inducing microorganisms. Analysis of the repertoire of used H chain Ig (V_H) genes by H-CDR3 spectrotyping, cloning, and sequencing of V_H genes from murine intestinal IgA-producing plasma cells reveals a very restricted usage of V_H genes and multiple clonally related sequences. The restricted usage of V_H genes is a very consistent observation, and is observed for IgA plasma cells derived from B-1 or conventional B-2 cells from different mouse strains. Clonal patterns from all analyzed V_H gene sequences show mainly independently acquired somatic mutations in contrast to the clonal evolution patterns often observed as a consequence of affinity maturation in germinal center reactions in peripheral lymphoid organs and Peyer’s patches. Our data suggest a model of clonal expansion in which many mucosal IgA-producing B cells develop in the absence of affinity maturation. The affinity of most produced IgA might not be the most critical factor for its possible function to control the commensal organisms, but simply the abundance of large amounts of IgA that can bind with relatively unselected affinity to redundant epitopes on such organisms.

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