Antigen receptor editing in anti-DNA transitional B cells deficient for surface IgM.
In response to encounter with self-Ag, autoreactive B cells may undergo secondary L chain gene rearrangement (receptor editing) and change the specificity of their Ag receptor. Knowing at what differentiative stage(s) developing B cells undergo receptor editing is important for understanding how self-reactive B cells are regulated. In this study, in mice with Ig transgenes coding for anti-self (DNA) Ab, we report dsDNA breaks indicative of ongoing secondary L chain rearrangement not only in bone marrow cells with a pre-B/B cell phenotype but also in immature/transitional splenic B cells with little or no surface IgM (sIgM(-/low)). L chain-edited transgenic B cells were detectable in spleen but not bone marrow and were still found to produce Ab specific for DNA (and apoptotic cells), albeit with lower affinity for DNA than the unedited transgenic Ab. We conclude that L chain editing in anti-DNA-transgenic B cells is not only ongoing in bone marrow but also in spleen. Indeed, transfer of sIgM(-/low) anti-DNA splenic B cells into SCID mice resulted in the appearance of a L chain editor (Vlambdax) in the serum of engrafted recipients. Finally, we also report evidence for ongoing L chain editing in sIgM(low) transitional splenic B cells of wild-type mice.
Kiefer
Kerstin
K
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Nakajima
Pamela B
PB
Oshinsky
Jennifer
J
Seeholzer
Steven H
SH
Radic
Marko
M
Bosma
Gayle C
GC
Bosma
Melvin J
MJ
D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000276:immunology*; D000915:Antibody Affinity; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology*; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D017710:Lymphocyte Transfusion; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D000974:Antibodies, Antinuclear; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell