Journal of Neuroimmunology
Volume 229, Issue 1 , Pages 123-128 , 15 December 2010

LRRK2 is expressed in B-2 but not in B-1 B cells, and downregulated by cellular activation

  • Makoto Kubo

      Affiliations

    • Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
    • ,
  • Yoshiko Kamiya

      Affiliations

    • Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
    • ,
  • Ryuichi Nagashima

      Affiliations

    • Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
    • ,
  • Tatsunori Maekawa

      Affiliations

    • Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
    • ,
  • Koji Eshima

      Affiliations

    • Department of Immunology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
    • ,
  • Sadahiro Azuma

      Affiliations

    • Department of Laboratory Animal Science, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
    • ,
  • Etsuro Ohta

      Affiliations

    • Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
    • ,
  • Fumiya Obata

      Affiliations

    • Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
    • R & D Center for Cell Design, Institute for Regenerative Medicine and Cell Design, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
    • Corresponding Author InformationCorresponding author. Division of Immunology, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan. Tel.: +81 42 778 8215; fax: +81 42 778 8075.

Received 19 May 2010 ,Revised 22 July 2010 ,Accepted 23 July 2010.

References 

  1. Baba Y, Kuroiwa A, Uitti RJ, Wszolek ZK, Yamada T. Alterations of T-lymphocyte populations in Parkinson disease. Parkinsonism Relat. Disord. 2005;11:493–498
  2. Baumgarth N, Herman OC, Jager GC, Brown L, Herzenberg LA. Innate and acquired humoral immunities to influenza virus are mediated by distinct arms of the immune system. Proc. Natl. Acad. Sci. U.S.A. 1999;96:2250–2255
  3. Berland R, Wortis HH. Origins and functions of B-1 cells with notes on the role of CD5. Annu. Rev. Immunol. 2002;20:253–300
  4. Biskup S, Moore DJ, Rea A, Lorenz-Deperieux B, Coombes CE, Dawson VL, et al. Dynamic and redundant regulation of LRRK2 and LRRK1 expression. BMC Neurosci. 2007;8:102
  5. Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J. Clin. Invest. 2009;119:182–192
  6. Dasu T, Sindhava V, Clarke SH, Bondada S. CD19 signaling is impaired in murine peritoneal and splenic B-1 B lymphocytes. Mol. Immunol. 2009;46:2655–2665
  7. Deng J, Lewis PA, Greggio E, Sluch E, Beilina A, Cookson MR. Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase. Proc. Natl. Acad. Sci. U.S.A. 2008;105:1499–1504
  8. Double KL, Rowe DB, Carew-Jones FM, Hayes M, Chan DK, Blackie J, et al. Anti-melanin antibodies are increased in sera in Parkinson's disease. Exp. Neurol. 2009;217:297–301
  9. Durand CA, Hartvigsen K, Fogelstrand L, Kim S, Iritani S, Vanhaesebroeck B, et al. Phosphoinositide 3-kinase p110 delta regulates natural antibody production, marginal zone and B-1 B cell function, and autoantibody responses. J. Immunol. 2009;183:5673–5684
  10. Fagarasan S, Shinkura R, Kamata T, Nogaki F, Ikuta K, Tashiro K, et al. Alymphoplasia (aly)-type nuclear factor kappaB-inducing kinase (NIK) causes defects in secondary lymphoid tissue chemokine receptor signaling and homing of peritoneal cells to the gut-associated lymphatic tissue system. J. Exp. Med. 2000;191:1477–1486
  11. Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F. A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2–q13.1. Ann. Neurol. 2002;51:296–301
  12. Funayama M, Hasegawa K, Ohta E, Kawashima N, Komiyama M, Kowa H, et al. An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family. Ann. Neurol. 2005;57:918–921
  13. Gandhi PN, Wang X, Zhu X, Chen SG, Wilson-Delfosse AL. The Roc domain of leucine-rich repeat kinase 2 is sufficient for interaction with microtubules. J. Neurosci. Res. 2008;86:1711–1720
  14. Gulley ML, Ogata LC, Thorson JA, Dailey MO, Kemp JD. Identification of a murine pan-T cell antigen which is also expressed during the terminal phases of B cell differentiation. J. Immunol. 1988;140:3751–3757
  15. Hardy RR. B-1 B cells: development, selection, natural autoantibody and leukemia. Curr. Opin. Immunol. 2006;18:547–555
  16. Hardy RR, Hayakawa K. B cell development pathways. Annu. Rev. Immunol. 2001;19:595–621
  17. Hayakawa K, Hardy RR, Parks DR, Herzenberg LA. The “Ly-1 B” cell subpopulation in normal immunodefective, and autoimmune mice. J. Exp. Med. 1983;157:202–218
  18. Hayakawa K, Hardy RR, Honda M, Herzenberg LA, Steinberg AD. Ly-1 B cells: functionally distinct lymphocytes that secrete IgM autoantibodies. Proc. Natl. Acad. Sci. U.S.A. 1984;81:2494–2498
  19. Hein K, Lorenz MG, Siebenkotten G, Petry K, Christine R, Radbruch A. Processing of switch transcripts is required for targeting of antibody class switch recombination. J. Exp. Med. 1998;188:2369–2374
  20. Herzenberg LA. B-1 cells: the lineage question revisited. Immunol. Rev. 2000;175:9–22
  21. Higashi S, Biskup S, West AB, Trinkaus D, Dawson VL, Faull RL, et al. Localization of Parkinson's disease-associated LRRK2 in normal and pathological human brain. Brain Res. 2007;1155:208–219
  22. Higashi S, Moore DJ, Colebrooke RE, Biskup S, Dawson VL, Arai H, et al. Expression and localization of Parkinson's disease-associated leucine-rich repeat kinase 2 in the mouse brain. J. Neurochem. 2007;100:368–381
  23. Holodick NE, Tumang JR, Rothstein TL. Continual signaling is responsible for constitutive ERK phosphorylation in B-1a cells. Mol. Immunol. 2009;46:3029–3036
  24. Hsu CH, Chan D, Greggio E, Saha S, Guillily MD, Ferree A, et al. MKK6 binds and regulates expression of Parkinson's disease-related protein LRRK2. J. Neurochem. 2010;112:1593–1604
  25. Imai Y, Gehrke S, Wang HQ, Takahashi R, Hasegawa K, Oota E, et al. Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila. EMBO J. 2008;27:2432–2443
  26. Ito G, Okai T, Fujino G, Takeda K, Ichijo H, Katada T, et al. GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease. Biochemistry. 2007;46:1380–1388
  27. Jaleel M, Nichols RJ, Deak M, Campbell DG, Gillardon F, Knebel A, et al. LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity. Biochem. J. 2007;405:307–317
  28. Larsen K, Madsen LB. Sequence conservation between porcine and human LRRK2. Mol. Biol. Rep. 2009;36:237–243
  29. Maekawa T, Kubo M, Yokoyama I, Ohta E, Obata F. Age-dependent and cell-population-restricted LRRK2 expression in normal mouse spleen. Biochem. Biophys. Res. Commun. 2010;392:431–435
  30. Melrose H, Lincoln S, Tyndall G, Dickson D, Farrer M. Anatomical localization of leucine-rich repeat kinase 2 in mouse brain. Neuroscience. 2006;139:791–794
  31. Meylan E, Tschopp J. The RIP kinases: crucial integrators of cellular stress. Trends Biochem. Sci. 2005;30:151–159
  32. Miyawaki S, Nakamura Y, Suzuka H, Koba M, Yasumizu R, Ikehara S, et al. A new mutation, aly, that induces a generalized lack of lymph nodes accompanied by immunodeficiency in mice. Eur. J. Immunol. 1994;24:429–434
  33. Orr CF, Rowe DB, Mizuno Y, Mori H, Halliday GM. A possible role for humoral immunity in the pathogenesis of Parkinson's disease. Brain. 2005;128:2665–2674
  34. Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron. 2004;44:595–600
  35. Rosenstein Y, Santana A, Pedraza-Alva G. CD43, a molecule with multiple functions. Immunol. Res. 1999;20:89–99
  36. Shinkura R, Kitada K, Matsuda F, Tashiro K, Ikuta K, Suzuki M, et al. Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase. Nat. Genet. 1999;22:74–77
  37. Simon-Sanchez J, Herranz-Perez V, Olucha-Bordonau F, Perez-Tur J. LRRK2 is expressed in areas affected by Parkinson's disease in the adult mouse brain. Eur. J. Neurosci. 2006;23:659–666
  38. Smith WW, Pei Z, Jiang H, Dawson VL, Dawson TM, Ross CA. Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat. Neurosci. 2006;9:1231–1233
  39. Tan EK, Sie L, Loong S. Growth rate of patient-derived lymphoblastoid cells with LRRK2 mutations. Mol. Genet. Metab. 2008;95:113
  40. Wells SM, Kantor AB, Stall AM. CD43 (S7) expression identifies peripheral B cell subsets. J. Immunol. 1994;153:5503–5515
  41. West AB, Moore DJ, Choi C, Andrabi SA, Li X, Dikeman D, et al. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. Hum. Mol. Genet. 2007;16:223–232
  42. Westerlund M, Belin AC, Anvret A, Bickford P, Olson L, Galter D. Developmental regulation of leucine-rich repeat kinase 1 and 2 expression in the brain and other rodent and human organs: implications for Parkinson's disease. Neuroscience. 2008;152:429–436
  43. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004;44:601–607

PII: S0165-5728(10)00334-6

doi: 10.1016/j.jneuroim.2010.07.021

Journal of Neuroimmunology
Volume 229, Issue 1 , Pages 123-128 , 15 December 2010

Article Tools

* Image Usage & Resolution