Somatic Deficiency of the Human E3 Ubiquitin Ligase Cbl in Leukocytes Impairs B Cell But Not T Cell Development and Function

Somatic Deficiency of the Human E3 Ubiquitin Ligase Cbl in Leukocytes Impairs B Cell But Not T Cell Development and Function Publisher Pubmed

Vatovec T ; Neehus AL ; Jackson KJL ; Avery DT ; Bagaric I ; Erazo L ; Arangofranco CA ; Ogishi M ; Ahmed SF ; Cederholm A ; Russell AJ ; Della Mina E ; Alrifai D ; Bull R Show All Authors

Vatovec T
Neehus AL
Jackson KJL
Avery DT
Bagaric I
Erazo L
Arangofranco CA
Ogishi M
Ahmed SF
Cederholm A
Russell AJ
Della Mina E
Alrifai 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
Soudee C
Delabesse E
Goulvestre C
Shahrooei M
Puel A
Andre I
Bolefeysot C
Abel L
Erlacher M
Beziat V
Lagreslepeyrou 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

Source: Nature Immunology Published:2026

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. © The Author(s) 2026.

Related Docs

1. E3 Ubiquitin Ligase Casitas B Lineage Lymphoma-B and Its Potential Therapeutic Implications for Immunotherapy, Clinical and Experimental Immunology (2021)

Style	Citing Format
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.
APA	Vatovec T, Neehus AL, Jackson KJL, Avery DT, Bagaric I, Erazo L, Arangofranco CA, Ogishi M, Ahmed SF, Cederholm A, Russell AJ, Della Mina E, Alrifai D, Bull R, Buetow L, Sobrino S, Zhang A, Wahlster L, Michelet M, ... Bohlen J (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.
Chicago	Vatovec T, Neehus AL, Jackson KJL, Avery DT, Bagaric I, Erazo L, Arangofranco CA, 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 27, no. 2 (2026): 308-322.
Harvard	Vatovec T 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), pp. 308-322.
Vancouver	Vatovec T, Neehus AL, Jackson KJL, Avery DT, Bagaric I, Erazo L, 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. 2026;27(2):308-322.
BibTex	@article{ author = {Vatovec T and Neehus AL and Jackson KJL and Avery DT and Bagaric I and Erazo L and Arangofranco CA and Ogishi M and Ahmed SF and Cederholm A and Russell AJ and Della Mina E and Alrifai D and Bull R and Buetow L and Sobrino S and Zhang A and Wahlster L and Michelet M and Parvaneh N and Peel J and Barzaghi F and Leardini D and Philippot Q and Saettini F and Dutrieux J and De Muylder B and Vendemini F and Baccelli F and Catala A and Gambineri E and Veltroni M and Pandiarajan V and Aguilar Y and Haerynck F and Elliott M and Turville S and Brillot F and Khan T and Consonni F and Berteloot L and Sewell WA and Rao G and Largeaud L and Conti F and Roullion C and Masson C and Pegoraro F and Ye T and Joubran S and Villalpando E and Bessot B and Seeleuthner Y and Le Voyer T and Rosain J and Li H and Janda Z and Muratore E and Soudee C and Delabesse E and Goulvestre C and Shahrooei M and Puel A and Andre I and Bolefeysot C and Abel L and Erlacher M and Beziat V and Lagreslepeyrou C and Cheynier R and Six E and Marr N and Pasquet M and Alsina L and Goodnow CC and Landegren N and Aiuti A and Zhang P and Masetti R and Huang DT and Ma CS and Casanova JL and Sankaran VG and Bustamante J and Tangye SG and Bohlen J}, title = {Somatic Deficiency of the Human E3 Ubiquitin Ligase Cbl in Leukocytes Impairs B Cell But Not T Cell Development and Function}, journal = {Nature Immunology}, volume = {27}, number = {2}, pages = {308-322}, year = {2026} }
RIS	TY - JOUR AU - Vatovec T AU - Neehus AL AU - Jackson KJL AU - Avery DT AU - Bagaric I AU - Erazo L AU - Arangofranco CA AU - Ogishi M AU - Ahmed SF AU - Cederholm A AU - Russell AJ AU - Della Mina E AU - Alrifai D AU - Bull R AU - Buetow L AU - Sobrino S AU - Zhang A AU - Wahlster L AU - Michelet M AU - Parvaneh N AU - Peel J AU - Barzaghi F AU - Leardini D AU - Philippot Q AU - Saettini F AU - Dutrieux J AU - De Muylder B AU - Vendemini F AU - Baccelli F AU - Catala A AU - Gambineri E AU - Veltroni M AU - Pandiarajan V AU - Aguilar Y AU - Haerynck F AU - Elliott M AU - Turville S AU - Brillot F AU - Khan T AU - Consonni F AU - Berteloot L AU - Sewell WA AU - Rao G AU - Largeaud L AU - Conti F AU - Roullion C AU - Masson C AU - Pegoraro F AU - Ye T AU - Joubran S AU - Villalpando E AU - Bessot B AU - Seeleuthner Y AU - Le Voyer T AU - Rosain J AU - Li H AU - Janda Z AU - Muratore E AU - Soudee C AU - Delabesse E AU - Goulvestre C AU - Shahrooei M AU - Puel A AU - Andre I AU - Bolefeysot C AU - Abel L AU - Erlacher M AU - Beziat V AU - Lagreslepeyrou C AU - Cheynier R AU - Six E AU - Marr N AU - Pasquet M AU - Alsina L AU - Goodnow CC AU - Landegren N AU - Aiuti A AU - Zhang P AU - Masetti R AU - Huang DT AU - Ma CS AU - Casanova JL AU - Sankaran VG AU - Bustamante J AU - Tangye SG AU - Bohlen J TI - Somatic Deficiency of the Human E3 Ubiquitin Ligase Cbl in Leukocytes Impairs B Cell But Not T Cell Development and Function JO - Nature Immunology VL - 27 IS - 2 SP - 308 EP - 322 PY - 2026 ER -

Style

Citing Format

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.

APA

Vatovec T, Neehus AL, Jackson KJL, Avery DT, Bagaric I, Erazo L, Arangofranco CA, Ogishi M, Ahmed SF, Cederholm A, Russell AJ, Della Mina E, Alrifai D, Bull R, Buetow L, Sobrino S, Zhang A, Wahlster L, Michelet M, ... Bohlen J (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.

Chicago

Vatovec T, Neehus AL, Jackson KJL, Avery DT, Bagaric I, Erazo L, Arangofranco CA, 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 27, no. 2 (2026): 308-322.

Harvard

Vatovec T 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), pp. 308-322.

Vancouver

Vatovec T, Neehus AL, Jackson KJL, Avery DT, Bagaric I, Erazo L, 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. 2026;27(2):308-322.

BibTex

@article{ author = {Vatovec T and Neehus AL and Jackson KJL and Avery DT and Bagaric I and Erazo L and Arangofranco CA and Ogishi M and Ahmed SF and Cederholm A and Russell AJ and Della Mina E and Alrifai D and Bull R and Buetow L and Sobrino S and Zhang A and Wahlster L and Michelet M and Parvaneh N and Peel J and Barzaghi F and Leardini D and Philippot Q and Saettini F and Dutrieux J and De Muylder B and Vendemini F and Baccelli F and Catala A and Gambineri E and Veltroni M and Pandiarajan V and Aguilar Y and Haerynck F and Elliott M and Turville S and Brillot F and Khan T and Consonni F and Berteloot L and Sewell WA and Rao G and Largeaud L and Conti F and Roullion C and Masson C and Pegoraro F and Ye T and Joubran S and Villalpando E and Bessot B and Seeleuthner Y and Le Voyer T and Rosain J and Li H and Janda Z and Muratore E and Soudee C and Delabesse E and Goulvestre C and Shahrooei M and Puel A and Andre I and Bolefeysot C and Abel L and Erlacher M and Beziat V and Lagreslepeyrou C and Cheynier R and Six E and Marr N and Pasquet M and Alsina L and Goodnow CC and Landegren N and Aiuti A and Zhang P and Masetti R and Huang DT and Ma CS and Casanova JL and Sankaran VG and Bustamante J and Tangye SG and Bohlen J}, title = {Somatic Deficiency of the Human E3 Ubiquitin Ligase Cbl in Leukocytes Impairs B Cell But Not T Cell Development and Function}, journal = {Nature Immunology}, volume = {27}, number = {2}, pages = {308-322}, year = {2026} }

RIS

TY - JOUR
AU - Vatovec T
AU - Neehus AL
AU - Jackson KJL
AU - Avery DT
AU - Bagaric I
AU - Erazo L
AU - Arangofranco CA
AU - Ogishi M
AU - Ahmed SF
AU - Cederholm A
AU - Russell AJ
AU - Della Mina E
AU - Alrifai D
AU - Bull R
AU - Buetow L
AU - Sobrino S
AU - Zhang A
AU - Wahlster L
AU - Michelet M
AU - Parvaneh N
AU - Peel J
AU - Barzaghi F
AU - Leardini D
AU - Philippot Q
AU - Saettini F
AU - Dutrieux J
AU - De Muylder B
AU - Vendemini F
AU - Baccelli F
AU - Catala A
AU - Gambineri E
AU - Veltroni M
AU - Pandiarajan V
AU - Aguilar Y
AU - Haerynck F
AU - Elliott M
AU - Turville S
AU - Brillot F
AU - Khan T
AU - Consonni F
AU - Berteloot L
AU - Sewell WA
AU - Rao G
AU - Largeaud L
AU - Conti F
AU - Roullion C
AU - Masson C
AU - Pegoraro F
AU - Ye T
AU - Joubran S
AU - Villalpando E
AU - Bessot B
AU - Seeleuthner Y
AU - Le Voyer T
AU - Rosain J
AU - Li H
AU - Janda Z
AU - Muratore E
AU - Soudee C
AU - Delabesse E
AU - Goulvestre C
AU - Shahrooei M
AU - Puel A
AU - Andre I
AU - Bolefeysot C
AU - Abel L
AU - Erlacher M
AU - Beziat V
AU - Lagreslepeyrou C
AU - Cheynier R
AU - Six E
AU - Marr N
AU - Pasquet M
AU - Alsina L
AU - Goodnow CC
AU - Landegren N
AU - Aiuti A
AU - Zhang P
AU - Masetti R
AU - Huang DT
AU - Ma CS
AU - Casanova JL
AU - Sankaran VG
AU - Bustamante J
AU - Tangye SG
AU - Bohlen J
TI - Somatic Deficiency of the Human E3 Ubiquitin Ligase Cbl in Leukocytes Impairs B Cell But Not T Cell Development and Function
JO - Nature Immunology
VL - 27
IS - 2
SP - 308
EP - 322
PY - 2026
ER -

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