(免疫学课件)5.Bcelldevelopment知识介绍.pptVIP

Immunology -B Cell Development;Kenneth M. Murphy;Nat Immunol. 2008 Feb;9(2):203-15. doi: 10.1038/ni1555. Epub 2008 Jan 6. Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. Pongubala JM1, Northrup DL, Lancki DW, Medina KL, Treiber T, Bertolino E, Thomas M, Grosschedl R, Allman D, Singh H. ;Outline;Lymphocytes derive from hematopoietic stem cells in the bone marrow;The early stages of B-cell development are dependent on bone marrow stromal cells;Early stages of B cell development are orchestrated by gene regulatory networks of transcription factors and growth factor receptors.;The development of a B-lineage cell proceeds through several stages marked by the rearrangement and expression of the immunoglobulin genes.;Expression of surface proteins, receptors and transcription factors in B-cell development;A productively rearranged immunoglobulin gene is immediately expressed as a protein by the developing B cells.;Allelic exclusion in individual B cells The state in which only one of the two alleles of a gene is expressed in a diploid cells. It occurs both the heavy-chain locus and the light chain loci. ;Pre-B cells rearrange the light-chian locus and express cell-surface immunoglobulin;Light chain isotypic exclusion: the expression of one type of light chain- κ or λ –by an individual B cell. The ratios of κ vs. λ expressing mature B cells vary in different species. In mice and rats it is 95% κ to 5% λ. In humans it is 65% κ to 35% λ. The aberrant ratio can indicate the presence of a lymphoproliferative disorder, which may be malignant.;Expression of proteins involved in gene rearrangement and the production of pre-B cell and B-cell receptors.;The steps in immunoglobulin gene rearrangement at which developing B cells can be lost.;Immature B cells are tested for autoreativity before they leave the bone marrow.;Replacement of light chains by receptor editing can rescue some self-reactive B cells by ch