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Blood, 15 September 2005, Vol. 106, No. 6, pp. 1891-1892. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lane, P. Search for Related Content PubMed Articles by Lane, P. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES Comment on Hardtke et al, page 1924 Where you are is what you are Peter Lane MRC CENTRE FOR IMMUNE REGULATION In this issue, Hardtke and colleagues conclusively demonstrate that expression on T cells of the B-cell–associated chemokine receptor, CXCR5, is essential for migration into B follicles (follicular B helper T cells [TFH]) and, further, that T cells are excluded from B follicles by the T cells' expression of the T-zone–associated chemokine, CCR7. Band T cells are normally segregated within lymphoid tissue by chemokine gradients that are established by local populations of lymphoid stromal cells. CXCR5+ B cells are attracted to the areas forming B follicles, whereas both CCR7+ T cells and antigen-presenting dendritic cells are attracted to sites that form T zones. This isolation of B cells from T-cell areas is essential for the production of high-affinity antibodies, as it excludes T cells of irrelevant specificities from the B follicle in which B-cell selection by "licensed" TFH occurs. As others have found,1 induction of CXCR5 on T cells occurs rapidly following priming and identifies cells destined to provide help in B follicles but not inflammatory responses. Although CXCR5 is expressed on a substantial fraction of primed T cells, many such cells continue to coexpress CCR7, an expression motif that localizes them at the B–T interface where the chemokine gradients establishing the B follicle and T zone compete for influence. Since activated CXCR5-expressing B cells mirror the situation in T cells by up-regulating CCR7,2 they too localize at the B–T interface, an arrangement likely to optimize the efficiency of B–T collaboration not only for primary antibody production but also for memory responses. Only a minority of CXCR5+CCR7+-expressing T cells go on to down-regulate CCR7 and become mature TFH where they foster the development of B-cell germinal centers, the structures within which affinity maturation of the B-cell response occurs. It is not certain which signals induce T cells to do this; perhaps the signals arise from some as-yet-unidentified interaction with antigen-activated B cells. One very interesting observation from Hardtke et al is that dual CXCR5+CCR7+-expressing T cells appear in lymph nodes where there is no obvious ongoing B-cell response (see figure), suggesting that these T cells might have migrated there following priming elsewhere. This possibility is supported by the fact that these T cells are found in blood.3 I think that these are recirculating memory cells primed to provide B-cell help and that their dual expression of CXCR5+CCR7+ guides them to a CD4+CD3- non–dendritic cell located at the B–T interface.4 My colleagues and I have found that the development and persistence of T memory cells that provide help to B cells depend on OX40 (CD134) and CD30 survival signals from these cells.5 The location of the T memory cells at the B–T interface puts them in pole position to provide rapid help to B cells at the earliest sign of reinfection, but the theory remains to be tested. View larger version (58K): [in this window] [in a new window]   Expression of CXCR5 and CCR7 and positioning of T cells to B-cell follicles in LNs and PPs. See the complete figure in the article beginning on page 1924.   References Campbell DJ, Kim CH, Butcher EC. Separable effector T cell populations specialized for B cell help or tissue inflammation. Nat Immunol. 2001;2: 876-881.[CrossRef][Medline] [Order article via Infotrieve] Reif K, Ekland EH, Ohl L, et al. Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position. Nature. 2002;416: 94-99.[CrossRef][Medline] [Order article via Infotrieve] Breitfeld D, Ohl L, Kremmer E, et al. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production [In Process Citation]. J Exp Med. 2000;192: 1545-1552.[Abstract/Free Full Text] Kim MY, Gaspal FM, Wiggett HE, et al. CD4(+)CD3(-) accessory cells costimulate primed CD4 T cells through OX40 and CD30 at sites where T cells collaborate with B cells. Immunity. 2003;18: 643-654.[CrossRef][Medline] [Order article via Infotrieve] Gaspal FM, Kim MY, McConnell FM, Raykundalia C, Bekiaris V, Lane PJ. Mice deficient in OX40 and CD30 signals lack memory antibody responses because of deficient CD4 T cell memory. J Immunol. 2005;174: 3891-3896.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help Svenja Hardtke, Lars Ohl, and Reinhold Förster Blood 2005 106: 1924-1931. [Abstract] [Full Text] [PDF] This article has been cited by other articles: L. Quintanilla-Martinez, S. Pittaluga, C. Miething, M. Klier, M. Rudelius, T. Davies-Hill, N. Anastasov, A. Martinez, A. Vivero, J. Duyster, et al. NPM-ALK-dependent expression of the transcription factor CCAAT/enhancer binding protein beta in ALK-positive anaplastic large cell lymphoma Blood, September 15, 2006; 108(6): 2029 - 2036. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lane, P. Search for Related Content PubMed Articles by Lane, P. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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