Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease.
Activation-induced cytidine deaminase (AID) expressed by germinal center B cells is a central regulator of somatic hypermutation (SHM) and class switch recombination (CSR). Humans with AID mutations develop not only the autosomal recessive form of hyper-IgM syndrome (HIGM2) associated with B cell hy...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-08-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0003033 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849332096152109056 |
|---|---|
| author | Koji Hase Daisuke Takahashi Masashi Ebisawa Sayaka Kawano Kikuji Itoh Hiroshi Ohno |
| author_facet | Koji Hase Daisuke Takahashi Masashi Ebisawa Sayaka Kawano Kikuji Itoh Hiroshi Ohno |
| author_sort | Koji Hase |
| collection | DOAJ |
| description | Activation-induced cytidine deaminase (AID) expressed by germinal center B cells is a central regulator of somatic hypermutation (SHM) and class switch recombination (CSR). Humans with AID mutations develop not only the autosomal recessive form of hyper-IgM syndrome (HIGM2) associated with B cell hyperplasia, but also autoimmune disorders by unknown mechanisms. We report here that AID-/- mice spontaneously develop tertiary lymphoid organs (TLOs) in non-lymphoid tissues including the stomach at around 6 months of age. At a later stage, AID-/- mice develop a severe gastritis characterized by loss of gastric glands and epithelial hyperplasia. The disease development was not attenuated even under germ-free (GF) conditions. Gastric autoantigen -specific serum IgM was elevated in AID-/- mice, and the serum levels correlated with the gastritis pathological score. Adoptive transfer experiments suggest that autoimmune CD4+ T cells mediate gastritis development as terminal effector cells. These results suggest that abnormal B-cell expansion due to AID deficiency can drive B-cell autoimmunity, and in turn promote TLO formation, which ultimately leads to the propagation of organ-specific autoimmune effector CD4+ T cells. Thus, AID plays an important role in the containment of autoimmune diseases by negative regulation of autoreactive B cells. |
| format | Article |
| id | doaj-art-1b044110e3f141c2b7bd9275be0eb3cf |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2008-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-1b044110e3f141c2b7bd9275be0eb3cf2025-08-20T03:46:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-08-0138e303310.1371/journal.pone.0003033Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease.Koji HaseDaisuke TakahashiMasashi EbisawaSayaka KawanoKikuji ItohHiroshi OhnoActivation-induced cytidine deaminase (AID) expressed by germinal center B cells is a central regulator of somatic hypermutation (SHM) and class switch recombination (CSR). Humans with AID mutations develop not only the autosomal recessive form of hyper-IgM syndrome (HIGM2) associated with B cell hyperplasia, but also autoimmune disorders by unknown mechanisms. We report here that AID-/- mice spontaneously develop tertiary lymphoid organs (TLOs) in non-lymphoid tissues including the stomach at around 6 months of age. At a later stage, AID-/- mice develop a severe gastritis characterized by loss of gastric glands and epithelial hyperplasia. The disease development was not attenuated even under germ-free (GF) conditions. Gastric autoantigen -specific serum IgM was elevated in AID-/- mice, and the serum levels correlated with the gastritis pathological score. Adoptive transfer experiments suggest that autoimmune CD4+ T cells mediate gastritis development as terminal effector cells. These results suggest that abnormal B-cell expansion due to AID deficiency can drive B-cell autoimmunity, and in turn promote TLO formation, which ultimately leads to the propagation of organ-specific autoimmune effector CD4+ T cells. Thus, AID plays an important role in the containment of autoimmune diseases by negative regulation of autoreactive B cells.https://doi.org/10.1371/journal.pone.0003033 |
| spellingShingle | Koji Hase Daisuke Takahashi Masashi Ebisawa Sayaka Kawano Kikuji Itoh Hiroshi Ohno Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease. PLoS ONE |
| title | Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease. |
| title_full | Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease. |
| title_fullStr | Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease. |
| title_full_unstemmed | Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease. |
| title_short | Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease. |
| title_sort | activation induced cytidine deaminase deficiency causes organ specific autoimmune disease |
| url | https://doi.org/10.1371/journal.pone.0003033 |
| work_keys_str_mv | AT kojihase activationinducedcytidinedeaminasedeficiencycausesorganspecificautoimmunedisease AT daisuketakahashi activationinducedcytidinedeaminasedeficiencycausesorganspecificautoimmunedisease AT masashiebisawa activationinducedcytidinedeaminasedeficiencycausesorganspecificautoimmunedisease AT sayakakawano activationinducedcytidinedeaminasedeficiencycausesorganspecificautoimmunedisease AT kikujiitoh activationinducedcytidinedeaminasedeficiencycausesorganspecificautoimmunedisease AT hiroshiohno activationinducedcytidinedeaminasedeficiencycausesorganspecificautoimmunedisease |