IgA subclass switch recombination in human mucosal and systemic immune compartments

Abstract

Human immunoglobulin A (IgA) comprises two IgA subclasses, IgA1 and IgA2, whose distribution has been shown by immunohistochemistry to be different in various body compartments. In comparison with systemic immune compartments, we investigated the IgA switch profiles at the molecular level in salivary and lacrimal glands, nasal mucosa, and proximal and distal gut mucosa. Direct switching from IgM to IgA1 or IgA2 predominated in all immune compartments analyzed. Similar composition of the Sμ-Sα1 and Sμ-Sα2 junctions was observed, including microhomology usage, which suggested that there is no major difference in the actual recombination mechanism utilized during IgA subclass switching. The proportion of IgA1/IgA2 switch recombination events largely paralleled the previously published immunohistochemical representation of IgA1(+) and IgA2(+) plasma cells, implying that the local subclass distribution generally reflects precommitted memory/effector B cells that have undergone IgA subclass switching before extravasation at the effector site. The extremely low or undetectable levels of activation-induced cytidine deaminase (AID) and Iα-Cμ circle transcripts in intestinal lamina propria samples as compared with Peyer's patches suggest that the cellular IgA subclass distribution outside of organized gut-associated lymphoid tissue is only to a minor extent, if at all, influenced by in situ switching.