Germinal center checkpoints in B cell tolerance in 3H9 transgenic mice.
Regulation throughout B cell maturation and activation prevents autoreactive B cells from entering germinal center (GC) reactions. This study shows that a subset of autoreactive B cells in V(H)3H9 micro IgH transgenic mice escapes these serial checkpoints and proceeds into splenic GC. GC B cells isolated from these mice all express the transgenic V(H)3H9 micro heavy chain, some co-express light chains that yield an anti-dsDNA specificity and some have somatic mutations, consistent with their GC origin. Nonetheless, B cell tolerance is ultimately preserved as serum titers of anti-dsDNA antibodies are not elevated. These observations suggest that those autoreactive GC B cells that escaped earlier checkpoints and possibly also those cells that acquire autoreactivity de novo by mutating their antigen receptor are arrested within the splenic GC before differentiating further into antibody-secreting plasma cells.
Paul
Elahna
E
Department of Pediatrics, Harvard Medical School, Division of Nephrology, Children's Hospital and Center for Blood Research, Boston, MA 02115, USA. elahna.paul@tch.harvard.edu
Lutz
Johannes
J
Erikson
Jan
J
Carroll
Michael C
MC
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000235:genetics; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D013154:Spleen / Q000166:cytology* / Q000276:immunology
D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains