본문으로 건너뛰기
← 뒤로

Somatic deficiency of the human E3 ubiquitin ligase CBL in leukocytes impairs B cell but not T cell development and function.

Nature immunology 2026 Vol.27(2) p. 308-322

Vatovec T, Neehus AL, Jackson KJL, Avery DT, Bagarić I, Erazo L, Arango-Franco CA, Ogishi M, Ahmed SF, Cederholm A, Russell AJ, Della Mina E, Al-Rifai D, Bull R, Buetow L, Sobrino S, Zhang A, Wahlster L, Michelet M, Parvaneh N, Peel J, Barzaghi F, Leardini D, Philippot Q, Saettini F, Dutrieux J, de Muylder B, Vendemini F, Baccelli F, Catala A, Gambineri E, Veltroni M, Pandiarajan V, Aguilar Y, Haerynck F, Elliott M, Turville S, Brillot F, Khan T, Consonni F, Berteloot L, Sewell WA, Rao G, Largeaud L, Conti F, Roullion C, Masson C, Pegoraro F, Ye T, Joubran S, Villalpando E, Bessot B, Seeleuthner Y, Le Voyer T, Rosain J, Li H, Janda Z, Muratore E, Soudée C, Delabesse E, Goulvestre C, Shahrooei M, Puel A, André I, Bole-Feysot C, Abel L, Erlacher M, Béziat V, Lagresle-Peyrou C, Cheynier R, Six E, Marr N, Pasquet M, Alsina L, Goodnow CC, Landegren N, Aiuti A, Zhang P, Masetti R, Huang DT, Ma CS, Casanova JL, Sankaran VG, Bustamante J, Tangye SG, Bohlen J

📝 환자 설명용 한 줄

The E3 ubiquitin ligase Casitas B-lineage lymphoma (CBL) promotes positive selection and antigen responses in mouse T lymphocytes by ubiquitinating ZAP70.

이 논문을 인용하기

BibTeX ↓ RIS ↓
APA Vatovec T, Neehus AL, et al. (2026). Somatic deficiency of the human E3 ubiquitin ligase CBL in leukocytes impairs B cell but not T cell development and function.. Nature immunology, 27(2), 308-322. https://doi.org/10.1038/s41590-025-02381-7
MLA Vatovec T, et al.. "Somatic deficiency of the human E3 ubiquitin ligase CBL in leukocytes impairs B cell but not T cell development and function.." Nature immunology, vol. 27, no. 2, 2026, pp. 308-322.
PMID 41540267

Abstract

The E3 ubiquitin ligase Casitas B-lineage lymphoma (CBL) promotes positive selection and antigen responses in mouse T lymphocytes by ubiquitinating ZAP70. Conversely, mouse CBL and CBL-B mutually redundantly regulate SYK ubiquitination and B cell receptor signaling. Here we studied individuals with somatically homozygous CBL loss-of-function variants in leukocytes. Human CBL is largely redundant for the development and function of human T cells. Conversely, B cell development is altered at the immature stage, with a tenfold increase in transitional cells, enhanced survival of autoreactive clones and impaired tolerance manifested by autoantibody production. B cell maturation is intrinsically impaired by reduced apoptosis and dysregulated B cell receptor signaling. CBL deficiency impairs humoral immunity by limiting memory B cell formation and reducing class switching and somatic hypermutation. Consequently, antigen-specific B cell generation and adaptive immune memory are disrupted, predisposing individuals to infection. Human CBL is critical for B cell development and function but redundant for T cell biology.

MeSH Terms

Humans; Proto-Oncogene Proteins c-cbl; T-Lymphocytes; B-Lymphocytes; Immunologic Memory; Signal Transduction; Cell Differentiation; Leukocytes; Animals; Receptors, Antigen, B-Cell; Immunity, Humoral; Female; Mice; Male