Synergistic cooperation and crosstalk betweenMYD88L265Pand mutations that dysregulate CD79B and surface IgM

Date

2017-09-04

Authors

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

Journal Title

Journal ISSN

Volume Title

Publisher

Rockefeller University Press

Abstract

CD79B andMYD88mutations 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 ofCD79BandMYD88L265Pmutations individually and combined in normal activated mouse B lymphocytes.CD79Bmutations alone increased surface IgM but did not enhance B cell survival, proliferation, or altered NF-κB responsive markers. Conversely, B cells expressingMYD88L265Pdecreased 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 ofMYD88L265PIn B cells chronically stimulated by self-antigen,CD79BandMYD88L265Pmutations 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 byMYD88L265Pand provide an explanation for the co-occurrence ofMYD88andCD79Bmutations in lymphomas.

Description

Keywords

animals, autoantibodies, autoantigens, b-lymphocytes, cd79 antigens, immunoglobulin m, lymphoma, b-cell, mice, mice, inbred c57bl, mice, transgenic, mutation, myeloid differentiation factor 88, receptor cross-talk

Citation

Source

The Journal of experimental medicine

Type

Journal article

Book Title

Entity type

Access Statement

Open Access

License Rights

DOI

10.1084/jem.20161454

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