Abstracts (complete list) - Wissenschaft Online

Gleb Turchinovich, Jan Kranich, Sonja Schmid, Jürgen Bachl, Jörg Kirberg
Kruppel-like factor 3 (KLF3) affects marginal zone B cell
differentiation
We have demonstrated that the hypermutating Abelson-leukemia virus induced pre-B
cell line 18-81 harbors a single provirus within the KLF3 locus, leading to constitutive
KLF3 expression. To study functions of KLF3 in B cells we generated transgenic mice
over-expressing KLF3 (CD19:KLF3).
Surprisingly, marginal zone (MZ) B cells were increased 3-10 fold in CD19:KLF3 mice.
To determine whether the increase is caused cell autonomously, competitive fetal liver
chimaeras were generated. Here, KLF3 over-expression did not affect the maturation of
FO B cells as these were derived from normal or CD19:KLF3 cells to the same extent as
they contributed to immature B cells, respectively. In contrast, the MZ B cell
compartment became almost exclusively dominated by CD19:KLF3 transgenic cells. To
ascertain that this altered lineage commitment occurs independent to receptor
specificity, CD19:KLF3 mice were crossed to B1-8H/3-83κ knock-in mice. Normally, B
cells expressing the B1-8H/3-83κ combination are mostly in the FO, while cells
expressing another light chain are enriched in the MZ. Strikingly, KLF3 over-expression
drives B1-8H/3-83κ expressing cells to mature extensively into the MZ lineage. Thus,
KLF3 activity alters MZ commitment independent of BCR receptor specificity. However,
no evidence of increased Ca++ mobilization, tyrosine-phosphorylation, or receptor
induced proliferation was detectable in KLF3 over-expressing B cells.
The KLF3 homologous factor KLF2/LKLF regulates S1P-R expression in T cells affecting
cell migration. We hypothesized that KLF3 over-expression in B cells similarly leads to
constitutive S1P-R expression and consequently enhanced B cell migration into/or
retention within the MZ. Normally, LPS stimulation leads to S1P-R down-regulation and
MZ B cell migration into the follicle. In contrast to our expectation, the migration of MZ
B cells into the follicle following LPS stimulation was unaffected in CD19:KLF3 transgenic
mice indicating that S1P-R expression is still under physiological control.
Thus, further experiments will focus on alternative pathway(s) known to modulate the
maturation of MZ and FO B cells.