Details

Autor(en) / Beteiligte

• Wang, James Q
• Jeelall, Yogesh S
• Humburg, Peter
• Batchelor, Emma L
• Kaya, Sarp M
• Yoo, Hee Min
• Goodnow, Christopher C
• Horikawa, Keisuke

Titel

Synergistic cooperation and crosstalk between MYD88 L265P and mutations that dysregulate CD79B and surface IgM

Ist Teil von

• The Journal of experimental medicine, 2017-09, Vol.214 (9), p.2759

Ort / Verlag

United States

Erscheinungsjahr

2017

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• and mutations are frequently and simultaneously detected in B cell malignancies. It is not known if these mutations cooperate or how crosstalk occurs. Here we analyze the consequences of and mutations individually and combined in normal activated mouse B lymphocytes. mutations alone increased surface IgM but did not enhance B cell survival, proliferation, or altered NF-κB responsive markers. Conversely, B cells expressing decreased surface IgM coupled with accumulation of endoglycosidase H-sensitive IgM intracellularly, resembling the trafficking block in anergic B cells repeatedly stimulated by self-antigen. Mutation or overexpression of CD79B counteracted the effect of In B cells chronically stimulated by self-antigen, and mutations in combination, but not individually, blocked peripheral deletion and triggered differentiation into autoantibody secreting plasmablasts. These results reveal that CD79B and surface IgM constitute a rate-limiting checkpoint against B cell dysregulation by and provide an explanation for the co-occurrence of and mutations in lymphomas.