Positive and negative selection events during B lymphopoiesis

Early in B-cell development, large numbers of cells have to be generated, each of which expresses only one type of B-cell receptor (i.e. Ig) on its surface. This is achieved by the surface expression of a pre-B cell receptor containing a μ heavy chains/surrogate light chain which differentially prov...

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Veröffentlicht in:Current opinion in immunology 1995-04, Vol.7 (2), p.214-227
Hauptverfasser: Melchers, Fritz, Rolink, Antonius, Grawunder, Ulf, Winkler, Thomas H, Karasuyama, Hajime, Ghia, Paolo, Andersson, Jan
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Sprache:eng
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Zusammenfassung:Early in B-cell development, large numbers of cells have to be generated, each of which expresses only one type of B-cell receptor (i.e. Ig) on its surface. This is achieved by the surface expression of a pre-B cell receptor containing a μ heavy chains/surrogate light chain which differentially provides signals for two responses of precursor B cells at this stage of development. On the one hand, it signals inhibition of further rearrangements of variable heavy chain to diverse-joining heavy chain loci to achieve allelic exclusion at the heavy-chain locus. On the other hand, it signals proliferative expansion by factors between 20 and 100. Later in B-cell development, tolerance to autoantigens must be established and maintained. Tolerance is achieved by developmental arrest and induction of secondary light-chain gene rearrangements in those IgM + immature B cells that are reactive to autoantigens presented in the primary B-cell generating organs. Even later in development, when mature surface (s)IgM +/sID + B cells encounter autoantigens presented to them in the periphery, either deletion or anergy of the autoantigen-reactive cells occurs. Anergic cells have a sIg-dependent, slg-proximal defect in signaling and are short-lived. Anergy can be broken in vitro by polyclonal activation via ligation of CD40 in the presence of IL-4. A small part of the remaining immature B cells not reactive to autoantigens are selected to become mature, antigen-reactive slgM +/slgD + B cells. Molecules which might guide such positive selection of B cells still remain to be identified.
ISSN:0952-7915
1879-0372
DOI:10.1016/0952-7915(95)80006-9