Leucine-rich repeat kinase 2 is a regulator of B cell function, affecting homeostasis, BCR signaling, IgA production, and TI antigen responses

Makoto Kubo; Ryuichi Nagashima; Etsuro Ohta; Tatsunori Maekawa; Yumiko Isobe; Mitsue Kurihara; Koji Eshima; Kazuya Iwabuchi; Toshikuni Sasaoka; Sadahiro Azuma; Heather L Melrose; Matthew J Farrer; Fumiya Obata

doi:10.1016/j.jneuroim.2016.01.005

Leucine-rich repeat kinase 2 is a regulator of B cell function, affecting homeostasis, BCR signaling, IgA production, and TI antigen responses

J Neuroimmunol. 2016 Mar 15:292:1-8. doi: 10.1016/j.jneuroim.2016.01.005. Epub 2016 Jan 8.

Authors

Affiliations

¹ Division of Immunology, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan; Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan; Research Facility of Regenerative Medicine and Cell Design, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan. Electronic address: kuboma@kitasato-u.ac.jp.
² Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
³ Division of Immunology, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan; Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan; Research Facility of Regenerative Medicine and Cell Design, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
⁴ Laboratory of Molecular Signal Biology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
⁵ Department of Immunology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
⁶ Department of Laboratory Animal Science, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan; Department of Comparative and Experimental Medicine, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8585, Japan.
⁷ Department of Laboratory Animal Science, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
⁸ Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
⁹ Department of Medical Genetics, University of British Columbia, Vancouver, V6T 2B5, British Columbia, Canada.

PMID: 26943952
DOI: 10.1016/j.jneuroim.2016.01.005

Abstract

LRRK2 is the causal molecule of autosomal dominant familial Parkinson's disease. B2 cells express a much higher LRRK2 mRNA level than B1 cells. To reveal the function of LRRK2 in B cells, we analyzed B cell functions in LRRK2-knockout (LRRK2(-/-)) mice. LRRK2(-/-) mice had significantly higher counts of peritoneal B1 cells than wild-type mice. After BCR stimulation, phosphor-Erk1/2 of splenic B2 cells was enhanced to a higher degree in LRRK2(-/-) mice. LRRK2(-/-) mice had a significantly higher serum IgA level, and TNP-Ficoll immunization increased the titer of serum anti-TNP IgM antibody. LRRK2 may play important roles in B cells.

Keywords: B cell receptor signaling; B1 cell; B2 cell; IgA; Leucine-rich repeat kinase 2; TI antigen.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Animals
Antigens, CD / metabolism
B-Lymphocytes / classification
B-Lymphocytes / metabolism*
Enzyme-Linked Immunosorbent Assay
Ficoll / analogs & derivatives
Ficoll / immunology
Flow Cytometry
Homeostasis / genetics*
Immunoglobulin A / blood*
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
MAP Kinase Signaling System / immunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Peritoneal Cavity / cytology
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Proto-Oncogene Proteins c-akt / metabolism
RNA, Messenger / metabolism
Signal Transduction / genetics
Signal Transduction / physiology*
Spleen / cytology
Transforming Growth Factor beta1 / blood
Trinitrobenzenes / immunology

Substances

Antigens, CD
Immunoglobulin A
RNA, Messenger
TNP-ficoll
Transforming Growth Factor beta1
Trinitrobenzenes
Ficoll
Akt1 protein, mouse
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Lrrk2 protein, mouse
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins c-akt