Positive and negative selection events during B lymphopoiesis

Fritz Melchers, Antonius Rolink, Ulf Grawunder, Thomas H. Winkler, Hajime Karasuyama, Paolo Ghia, Jan Andersson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)214-227
Number of pages14
JournalCurrent Opinion in Immunology
Volume7
Issue number2
DOIs
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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