Bruton's tyrosine kinase is required for signaling the CD79b-mediated pro-B to pre-B cell transition

• Published in: International immunology 2001-04, Vol.13 (4), p.485-493
• Main Authors: Kouro, Taku, Nagata, Kisaburo, Takaki, Satoshi, Nisitani, Sazuku, Hirano, Masayuki, Wahl, Matthew I., Witte, Owen N., Karasuyama, Hajime, Takatsu, Kiyoshi
• Format: Article
• Language: English
• Subjects: Agammaglobulinaemia Tyrosine Kinase; Animals; Antigens, CD - immunology; B cell development; B-Lymphocytes - cytology; B-Lymphocytes - enzymology; B-Lymphocytes - immunology; Bruton's tyrosine kinase-deficient mice; BTK Bruton's tyrosine kinase; CD79 Antigens; CD79b antigen; Cell Differentiation; DKO double knockout; DNA-Binding Proteins; HRP horseradish peroxidase; Igβ; Isoenzymes - metabolism; ITAM immunoreceptor tyrosine-based activation motif; KLH keyhole limpet hemocyanin; KO knockout; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - metabolism; PH pleckstrin homology; Phospholipase C gamma; Phosphorylation; PLC phospholipase C; pre-BCR; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - physiology; RAG recombination-activating gene; Receptors, Antigen, B-Cell - immunology; recombination-activating gene-2-deficient mice; Signal Transduction; TH Tec homology; Type C Phospholipases - metabolism; Tyrosine - metabolism; XID X-linked immunodeficiency; XLA X-linked agammaglobulinemia
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/13.4.485

Formation of the pre-BCR complex is a critical check point during B cell development and induces the transition of pro-B to pre-B cells. CD79b (Igβ) is a signaling component in the pre-BCR complex, since differentiation to the pre-B phenotype is induced by cross-linking the CD79b expressed on developmentally arrested pro-B cells from recombination-activating gene (RAG)-2-deficient mice. Bruton's tyrosine kinase (BTK) plays important roles in B cell development. However, its molecular mechanisms in early B cell development are not fully understood. To examine whether BTK functions in CD79b-mediated signaling for the pro-B/pre-B transition, we utilized RAG2/BTK double-knockout (DKO) mice. Pro-B cells from RAG2/BTK-DKO mice did not differentiate into pre-B cells following CD79b cross-linking, although tyrosine phosphorylation of cellular proteins including Erk1/2 and phospholipase C-γ2 was induced in the same manner as RAG2-KO mice. BTK is phosphorylated after cross-linking of CD79b on RAG2-deficient pro-B cells. These findings suggest that BTK-dependent pathways downstream of CD79b are critical for the pro-B/pre-B transition and BTK-independent signaling pathways are also activated via the pre-BCR complex.