The Walter and Eliza Hall Institute of Medical Research

Associate Professor David Tarlinton

Details

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Division: Immunology

Research Overview

Immunising animals with a virus, a bacterium, a protein or a vaccine, generates an immunological memory that comprises long lived antibody secreting cells and recirculating memory cells. The antibody secreting cells persist for many years in bone marrow, while the quiescent memory B cells recirculate, but can be activated by re-exposure to the original antigen, rapidly increasing in number and differentiating into antibody secreting cells. Key proteins regulating lymphocyte differentiation and survival in response to antigen have been identified and understanding their activity in vivo, will be central to understanding the regulation of the immune system and the maintenance of immunological memory.

In some circumstances activation of the immune system is inappropriate and can cause or exacerbate auto-immune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Alterations in the manner in which B lymphocytes sense and respond to antigen are associated with the development of certain antibody-mediated autoimmune diseases. Analysis of B lymphocytes with such altered sensing provide insights into potential causes of disease and thus potential therapeutic targets.

Research Interests

• Plasma cell differentiation
• The formation and maintenance of immunological memory
• The role of Lyn tyrosine kinase in regulating B cell differentiation

Selected Publications

1. Huntington ND, Xu Y, Puthalakath H, Light A, Willis SN, Strasser A, Tarlinton DM. CD45 links the B cell receptor with cell survival and is required for the persistence of germinal centers. Nat Immunol. 2006 Feb;7(2):190-8 PMID: 16378097 [PubMed - indexed for MEDLINE]
2. Beavitt SJ, Harder KW, Kemp JM, Jones J, Quilici C, Casagranda F, Lam E, Turner D, Brennan S, Sly PD, Tarlinton DM, Anderson GP, Hibbs ML. Lyn-deficient mice develop severe, persistent asthma: Lyn is a critical negative regulator of Th2 immunity. J Immunol. 2005 Aug 1;175(3):1867-75 PMID: 16034130 [PubMed - indexed for MEDLINE]
3. Polli M, Dakic A, Light A, Wu L, Tarlinton DM, Nutt SL. The development of functional B lymphocytes in conditional PU.1 knock-out mice. Blood. 2005 Sep 15;106(6):2083-90 PMID: 15933053 [PubMed - indexed for MEDLINE]
4. Huntington ND, Xu Y, Nutt SL, Tarlinton DM. A requirement for CD45 distinguishes Ly49D-mediated cytokine and chemokine production from killing in primary natural killer cells. J Exp Med. 2005 May 2;201(9):1421-33 PMID: 15867094 [PubMed - indexed for MEDLINE]
5. Blink EJ, Light A, Kallies A, Nutt SL, Hodgkin PD, Tarlinton DM. Early appearance of germinal center-derived memory B cells and plasma cells in blood after primary immunization. J Exp Med. 2005 Feb 21;201(4):545-54 PMID: 15710653 [PubMed - indexed for MEDLINE]
6. Xu Y, Harder KW, Huntington ND, Hibbs ML, Tarlinton DM. Lyn tyrosine kinase: accentuating the positive and the negative. Immunity. 2005 Jan;22(1):9-18 PMID: 15664155 [PubMed - indexed for MEDLINE]
7. Kallies A, Hasbold J, Tarlinton DM, Dietrich W, Corcoran LM, Hodgkin PD, Nutt SL. Plasma cell ontogeny defined by quantitative changes in blimp-1 expression. J Exp Med. 2004 Oct 18;200(8):967-77 PMID: 15492122 [PubMed - indexed for MEDLINE]
8. Huntington ND, Tarlinton DM. CD45: direct and indirect government of immune regulation. Immunol Lett. 2004 Jul 15;94(3):167-74 PMID: 15275963 [PubMed - indexed for MEDLINE]
9. Tarlinton DM, Hodgkin PD. Targeting plasma cells in autoimmune diseases. J Exp Med. 2004 Jun 7;199(11):1451-4 PMID: 15173204 [PubMed - indexed for MEDLINE]
10. Hasbold J, Corcoran LM, Tarlinton DM, Tangye SG, Hodgkin PD. Evidence from the generation of immunoglobulin G-secreting cells that stochastic mechanisms regulate lymphocyte differentiation. Nat Immunol. 2004 Jan;5(1):55-63 PMID: 14647274 [PubMed - indexed for MEDLINE]

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Current Laboratory Members

Faculty Member: David Tarlinton, BSc(Hons) Syd PhD Stanford

Postdoctoral Fellow: Simona Infantino, PhD Bellinzoma

Postdoctoral Fellow: Kim Jacobson, BSc(Hons) Tech Syd PhD Syd

Postdoctoral Fellow: Katja Luethje, PhD Hamburg

Postdoctoral Fellow: Victor Peperzak, PhD Amsterdam

Postdoctoral Fellow: Ingela Vikstrom, MSc PhD Ume

Research Assistant: Amanda Light, BAppSc RMIT

Research Assistant: Kristy O'Donnell, BAppSc RMIT BSc(Hons) Melb

Research Assistant: Dimitra Zotos, BBiomedSc(Hons) Deakin