Leo D Wang | PubMed Health

PubMed2004

Selection of B lymphocytes in the periphery is determined by the functional capacity of the B cell antigen receptor.

Within the B cell antigen receptor (BCR), the cytoplasmic tails of both Igalpha and Igbeta are required for normal B cell development and maturation. To dissect the mechanisms by which each tail contributes to development in vivo, Igbeta(-/-) mice were reconstituted with retroviruses encoding either wild-type Igbeta, an Igbeta molecule lacking a cytoplasmic tail (Igbeta(deltaC)) or one in which the cytoplasmic tail was derived from Igalpha (Igbeta(Calpha)). All constructs rescued B cell development and generated immature B cell populations in the bone marrow with similar expression levels of both Igbeta and membrane-bound IgM. In the periphery, receptor-surface density was inversely proportional to the number of Igalpha tails in the BCR. Although peripheral-surface-receptor levels differed, splenic B cells expressing either Igbeta or Igbeta(Calpha) responded similarly to stimulation through the BCR. Analysis of membrane-bound IgM and Igbeta expression revealed that peripheral-receptor expression was primarily determined by positive selection between the bone marrow and peripheral immature B cell populations. These data indicate that B cells are selected into the periphery on the basis of a common level of antigen responsiveness.

Animals↗

PubMed2003

B-cell antigen-receptor signalling in lymphocyte development.

Signalling through the B-cell antigen receptor (BCR) is required throughout B-cell development and peripheral maturation. Targeted disruption of BCR components or downstream effectors indicates that specific signalling mechanisms are preferentially required for central B-cell development, peripheral maturation and repertoire selection. Additionally, the avidity and the context in which antigen is encountered determine both cell fate and differentiation in the periphery. Although the signalling and receptor components required at each stage have been largely elucidated, the molecular mechanisms through which specific signalling are evoked at each stage are still obscure. In particular, it is not known how the pre-BCR initiates the signals required for normal development or how immature B cells regulate the signalling pathways that determine cell fate. In this review, we will summarize the recent studies that have defined the molecules required for B-cell development and maturation as well as the theories on how signals may be regulated at each stage.

Animals↗