title: Axon growth and guidance genes identify T-dependent germinal centre B cells.
abstract: Selection of B cells subjected to hypermutation in germinal centres (GC) during T cell-dependent (TD) antibody responses yields memory cells and long-lived plasma cells that produce high affinity antibodies biased to foreign antigens rather than self-antigens. GC also form in T-independent (TI) responses to polysaccharide antigens but failed selection results in GC involution and memory cells are not generated. To date there are no markers that allow phenotypic distinction of T-dependent and TI germinal centre B cells. We compared the global gene expression of GC B cells purified from mice immunized with either TD or TI antigens and identified eighty genes that are differentially expressed in TD GC. Significantly, the largest cluster comprises genes involved in growth and guidance of neuron axons such as Plexin B2, Basp1, Nelf, Shh, Sc4mol and Sult4alpha. This is consistent with formation of long neurite (axon and dendrite)-like structures by mouse and human GC B cells, which may facilitate T:B cell interactions within GC, affinity maturation and B cell memory formation. Expression of BASP1 and PLEXIN B2 protein is very low or undetectable in resting and TI GC B cells, but markedly upregulated in GC B cells induced in the presence of T cell help. Finally we show some of the axon growth genes upregulated in TD-GC B cells including Basp1, Shh, Sult4alpha, Sc4mol are also preferentially expressed in post-GC B cell neoplasms.
authors.affiliation: Division of Immunology and Genetics, John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
authors.forename: Di
authors.initials: D
authors.lastname: Yu
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Cook
authors.forename: Dong-Mi
authors.initials: DM
authors.lastname: Shin
authors.forename: Diego G
authors.initials: DG
authors.lastname: Silva
authors.forename: Jennifer
authors.initials: J
authors.lastname: Marshall
authors.forename: Kai-Michael
authors.initials: KM
authors.lastname: Toellner
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Havran
authors.forename: Pico
authors.initials: P
authors.lastname: Caroni
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cooke
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.forename: Ian C M
authors.initials: IC
authors.lastname: MacLennan
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: Carola G
authors.initials: CG
authors.lastname: Vinuesa
mesh_terms: D000818:Animals; D000955:Antigens, T-Independent / Q000235:genetics* / Q000276:immunology; D001369:Axons / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D015322:Gene Rearrangement, B-Lymphocyte; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007945:Leukemia, Lymphoid / Q000235:genetics / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000235:genetics / Q000276:immunology; D051379:Mice; D009414:Nerve Growth Factors / Q000235:genetics / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D015238:Sulfotransferases; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: D000955:Antigens, T-Independent; C489363:Basp1 protein, mouse; D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D053823:Hedgehog Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C519231:Plxnb2 protein, mouse; C465570:Shh protein, mouse; D014157:Transcription Factors; C118437:negative elongation factor; C479953:SULT4A1 protein, human; D015238:Sulfotransferases