Axon growth and guidance genes identify T-dependent germinal centre B cells

Immunol Cell Biol. 2008 Jan;86(1):3-14. doi: 10.1038/sj.icb.7100123. Epub 2007 Oct 16.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, T-Independent / genetics*
  • Antigens, T-Independent / immunology
  • Axons / physiology
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • Calmodulin-Binding Proteins / genetics
  • Calmodulin-Binding Proteins / immunology
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / immunology
  • Gene Expression Regulation / immunology*
  • Gene Rearrangement, B-Lymphocyte
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / immunology
  • Humans
  • Immunologic Memory
  • Leukemia, Lymphoid / genetics
  • Leukemia, Lymphoid / immunology
  • Lymphocyte Cooperation / genetics
  • Lymphocyte Cooperation / immunology
  • Mice
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / immunology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology
  • Oligonucleotide Array Sequence Analysis
  • Organ Specificity
  • Sulfotransferases
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Transcription Factors / genetics
  • Transcription Factors / immunology

Substances

  • Antigens, T-Independent
  • Basp1 protein, mouse
  • Calmodulin-Binding Proteins
  • Cytoskeletal Proteins
  • Hedgehog Proteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Plxnb2 protein, mouse
  • Shh protein, mouse
  • Transcription Factors
  • negative elongation factor
  • SULT4A1 protein, human
  • Sulfotransferases