Single Round of Antigen Receptor Signaling Programs Naive B Cells to Receive T Cell Help

SummaryTo simulate transient B cell activation that is the likely initiator of T-dependent responses, we examined the molecular and functional consequences of a single round of immunoglobulin M (IgM) signaling. This form of activation triggered early cytosolic signaling and the transcription factor NF-κB activation indistinguishably from conventional continuous IgM crosslinking but did not induce G1 progression. However, single round IgM signaling changed the expression of chemokine and chemokine receptor genes implicated in initiating T-dependent responses, as well as accentuated responsiveness to CD40 signaling. Several features of single-round IgM signaling in vitro were recapitulated in B cells after short-term exposure to antigen in vivo. We propose that transient BCR signals prime B cells to receive T cell help by increasing the probability of B-T encounter and creating a cellular environment that is hyper-responsive to CD40 signaling.

► A single round of BCR signaling initiates long-term changes in B cell gene expression
► Activated genes include T cell-attracting chemokines
► Pulse-activation upregulates CCR7 and MHC-II expression
► Pulse-activated B cells are hyper-responsive to CD40 signaling