Checkpoints that control B cell development.
B cells differentiate from pluripotent hematopoietic stem cells (pHSCs) in a series of distinct stages. During early embryonic development, pHSCs migrate into the fetal liver, where they develop and mature to B cells in a transient wave, which preferentially populates epithelia and lung as well as gut-associated lymphoid tissues. This is followed by continuous B cell development throughout life in the bone marrow to immature B cells that migrate to secondary lymphoid tissues, where they mature. At early stages of development, before B cell maturation, the gene loci encoding the heavy and light chains of immunoglobulin that determine the B cell receptor composition undergo stepwise rearrangements of variable region-encoding gene segments. Throughout life, these gene rearrangements continuously generate B cell repertoires capable of recognizing a plethora of self-antigens and non-self-antigens. The microenvironment in which these B cell repertoires develop provide signaling molecules that play critical roles in promoting gene rearrangements, proliferation, survival, or apoptosis, and that help to distinguish self-reactive from non-self-reactive B cells at four distinct checkpoints. This refinement of the B cell repertoire directly contributes to immunity, and defects in the process contribute to autoimmune disease.
Fritz
F
Melchers
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology; D039904:Pluripotent Stem Cells / Q000276:immunology / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*
D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell