한빛사 논문
Wooseob Kima, Eunha Kimb,1, Hyungyu Mina, Min Gyu Kimb, Verena B. Eisenbeisc, Amit K. Duttac, Igor Pavlovicd, Henning J. Jessenc,e, Seyun Kimb,2, and Rho Hyun Seonga,2
a School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, 08826 Seoul, Korea; b Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 34141 Daejeon, Korea; c Institute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany; d Department of Chemistry, Technical University Munich, D-85748 Garching, Germany; and e Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany
1 Present address: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
2 To whom correspondence may be addressed.
Abstract
T cell-independent (TI) B cell response is critical for the early protection against pathogen invasion. The regulation and activation of Bruton’s tyrosine kinase (Btk) is known as a pivotal step of B cell antigen receptor (BCR) signaling in TI humoral immunity, as observed in patients with X-linked agammaglobulinemia (XLA) experiencing a high incidence of encapsulated bacterial infections. However, key questions remain as to whether a well-established canonical BCR signaling pathway is sufficient to regulate the activity of Btk. Here, we find that inositol hexakisphosphate (InsP6) acts as a physiological regulator of Btk in BCR signaling. Absence of higher order inositol phosphates (InsPs), inositol polyphosphates, leads to an inability to mount immune response against TI antigens. Interestingly, the significance of InsP6-mediated Btk regulation is more prominent in IgM+ plasma cells. Hence, the present study identifies higher order InsPs as principal components of B cell activation upon TI antigen stimulation and presents a mechanism for InsP-mediated regulation of the BCR signaling.
T cell-independent immune response, B cell antigen receptor, Bruton’s tyrosine kinase, inositol phosphate, inositol polyphosphate multikinase
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