Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells.
The production of class-switched antibodies, particularly immunoglobulin (Ig) G1 and IgE, occurs efficiently in T cell receptor (TCR) alpha-/- mice that are congenitally devoid of alpha/beta T cells. This finding runs counter to a wealth of data indicating that IgG1 and IgE synthesis are largely dependent on the collaboration between B and alpha/beta T cells. Furthermore, many of the antibodies synthesized in TCR alpha-/- mice are reactive to a similar spectrum of self-antigens as that targeted by autoantibodies characterizing human systemic lupus erythematosus (SLE). SLE, too, is most commonly regarded as an alpha/beta T cell-mediated condition. To distinguish whether the development of autoantibodies in TCR alpha-/- mice is due to an intrinsic de-regulation of B cells, or to a heretofore poorly characterized collaboration between B and "non-alpha/beta T" cells, the phenotype has been reconstituted by transfer of various populations of B and non-alpha/beta T cells including cloned gamma/delta T cells derived from TCR alpha-/- mice, to severe combined immunodeficient (SCID) mice. The results establish that the reproducible production of IgG1 (including autoantibodies) is a product of non-alpha/beta T cell help that can be provided by gamma/delta T cells. This type of B-T collaboration sustains the production of germinal centers, lymphoid follicles that ordinarily are anatomical signatures of alpha/beta T-B cell collaboration. Thus, non-alpha/beta T cell help may drive Ig synthesis and autoreactivity under various circumstances, especially in cases of alpha/beta T cell immunodeficiency.
Wen
L
L
Department of Biology, Yale University, New Haven, Connecticut 06520, USA.
Pao
W
W
Wong
F S
FS
Peng
Q
Q
Craft
J
J
Zheng
B
B
Kelsoe
G
G
Dianda
L
L
Owen
M J
MJ
Hayday
A C
AC
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D002999:Clone Cells; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007073:Immunoglobulin E