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IgA production without mu or delta chain expression in developing B cells.
A J Macpherson1, A Lamarre, K McCoy
1Institute of Experimental Immunology, Universitätsspital, Schmelzbergstrasse 12, CH8091 Zürich, Switzerland. amacpher@pathol.unizh.ch
Nature Immunology
|June 29, 2001
Summary
This study reveals a novel IgA production pathway in mice lacking IgM/IgD, suggesting an evolutionarily primitive immune system. Immature B cells may switch to IgA in peripheral tissues, bypassing conventional B cell development.
Area of Science:
- Immunology
- B cell biology
- Innate immunity
Background:
- Membrane-bound immunoglobulin M (IgM) and IgD expression are crucial for B cell differentiation and antibody production in mammals.
- Conventional B cell development involves heavy chain locus rearrangement in IgM+ B cells to express other antibody classes.
Purpose of the Study:
- To investigate B cell development and antibody production in mice lacking IgM and IgD expression (muMT mice).
- To characterize the function and regulation of IgA produced in the absence of conventional B cell signaling.
Main Methods:
- Analysis of B cell development and IgA expression in muMT mice.
- Assessment of muMT IgA binding to bacterial proteins and response to Salmonella infection.
- Investigation of the role of peripheral lymphoid tissues in this alternative IgA pathway.
Main Results:
- muMT mice selectively express IgA despite a pro-B cell developmental block and lack of IgM/IgD.
- This muMT IgA binds commensal intestinal bacteria and shows weak induction by Salmonella infection.
- The IgA production pathway depends on extrasplenic peripheral lymphoid tissues.
Conclusions:
- A primitive IgA production pathway exists in mammals, independent of conventional B cell development.
- Immature B cells may differentiate into IgA-producing cells in peripheral sites, particularly in the gut.
- This pathway highlights an alternative mechanism for mucosal immunity evolutionarily.