title: Leucine-rich repeat kinase 2 is a regulator of B cell function, affecting homeostasis, BCR signaling, IgA production, and TI antigen responses.
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.
authors.affiliation: 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.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nagashima
authors.affiliation: 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.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ohta
authors.affiliation: Laboratory of Molecular Signal Biology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Isobe
authors.affiliation: Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Mitsue
authors.initials: M
authors.lastname: Kurihara
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Eshima
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
authors.affiliation: 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.
authors.forename: Toshikuni
authors.initials: T
authors.lastname: Sasaoka
authors.affiliation: Department of Laboratory Animal Science, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Azuma
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Melrose
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, V6T 2B5, British Columbia, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.affiliation: 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.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Obata
mesh_terms: D000367:Age Factors; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000145:classification / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D005434:Flow Cytometry; D006706:Homeostasis / Q000235:genetics*; D007070:Immunoglobulin A / Q000097:blood*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010529:Peritoneal Cavity / Q000166:cytology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014301:Trinitrobenzenes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D007070:Immunoglobulin A; D012333:RNA, Messenger; C020529:TNP-ficoll; D053773:Transforming Growth Factor beta1; D014301:Trinitrobenzenes; D005362:Ficoll; C514862:Akt1 protein, mouse; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; C495279:Lrrk2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: B cell receptor signaling; B1 cell; B2 cell; IgA; Leucine-rich repeat kinase 2; TI antigen