Abstracts (complete list) - Wissenschaft Online

Sebastian Dütting, Wolfgang Schuh, Kai Hermann, Christiane Lang, Hans-Martin Jäck,
Dirk Mielenz
Function of Swiprosin-2/EFhd1 during B cell development
Functional peripheral B cell subsets are produced from hematopoietic stem cells. An
important early checkpoint of this process is the transient expression of the pre-B cell
receptor (pre-BCR) at the transition from the late progenitor B cell (pro-B) to the large
precursor B cell (pre-B) stage. The pre-BCR consists of a membrane-anchored HC of the
• isotype (•HC) associated with λ and VpreB, and drives pre B cells into a clonal
expansion phase of two to five cell divisions.
Swiprosin-2 (also: EFhd1/Mitocalcin) is a close homologue of Swiprosin-1/Efhd2, an
adaptor protein we showed recently to be involved in proximal B cell receptor signaling.
In contrast to Swiprosin-1 that was expressed in all murine B cell lines and primary B
cells examined, albeit at different levels, Swiprosin-2 protein and mRNA were only
expressed in a transformed pro-B-cell line (38B9) and in primary pro-B cells. We thus
hypothesized that Swiprosin-2 is down-regulated by the pre-BCR. Using a transgenic tetoff
system that allows inducible pre-BCR-expression in primary cells, we demonstrated
pre-BCR-dependent down-regulation of Swiprosin-2 on mRNA and protein level. We
corroborated this result with IL-7 dependent R5B pro-B cells and transformed 38B9 pro-
B cells either lacking or expressing a functional surface pre-BCR. A dysfunctional,
cytoplasmic •HC did not regulate Swiprosin-2 expression, demonstrating that only
signals from the surface pre-BCR induce Swiprosin-2 down-regulation. We hypothesize
that pre-BCR-induced down-regulation of murine Swiprosin-2 is required for pre-B cell
differentiation and/or proliferation. To test this hypothesis we are currently infecting
primary pro-B cells with a Swiprosin-2-encoding retrovirus that overcomes downregulation
of Swiprosin-2. In the future, we want to identify the function of Swiprosin-2
during B cell development and determine the mechanisms by which Swiprosin-2
potentially affects B cell development.