Immature B cells from neonatal mice show a selective inability to up-regulate MHC class II expression in response to antigen receptor ligation

Abstract

Immature and mature B cells show phenotypic and functional differences. Thus immature B cells are functionally unresponsive to stimuli including ligation of sIg and CD38 which induce proliferation in mature B cells. Furthermore, immature B cells have been widely shown to be hypersensitive to tolerance induction. To investigate the reasons for this differential responsiveness we have compared the ability of mature and immature B cells to show receptor-induced tyrosine phosphorylation of cellular substrates, a receptor-proximal response and MHC hyperexpression, which occurs later. Mature and neonatal a cells displayed a similar pattern of sIg-induced tyrosine phosphorylation and their responses had similar kinetics. Importantly, crosslinking of sIg on immature B cells induced tyrosine phosphorylation of substrates with mol. wt corresponding to the chains of the Igαβ dimer, which plays a critical role in B cell signalling. Immunofluorescence analysis showed that immature B cells constitutively express lower levels of MHC class II than their mature counterparts, consistent with previous studies. Here we report for the first time that immature B cells fail to hyperexpress class II after sIg ligation, although this response is induced by other stimuli. These observations suggest that the ability to up-regulate class II is developmentally regulated in the a cell lineage. Moreover, the selective failure of sIg-induced class II hyperexpression shown by immature a cells may not allow effective T-B cell collaboration and contribute to tolerance induction.