Notch2 Regulates Macrophage-Related Genes in Marginal Zone B Cells.

[Background] While Notch1 plays critical roles in early T cell development, Notch2 is indispensable for B cell development. Conditional inactivation of Notch2 in the hematopoietic compartment leads to loss of the marginal zone B (MZB) cells and defect in the particular fraction of follicular B (FOB) cells characterized as T2 B cells. Because of their position bordering the marginal sinuses and red pulp in the spleen, MZB cells are amongst the first cells that come in contact with blood-borne substances and thus thought to have critical roles in the defense against bacterial pathogens which are presumably scavenged in this anatomical site. Here we demonstrate that Notch2 regulates the expression of genes that specifically play a role in macrophages. [Methods] Splenic T2 B cells, supposed to contain precursors of MZB cells, were sorted from Notch2 conditional knockout (N2cKO) and wild type (WT) mouse and conveyed microarray analysis. Then, different fractions of B cells in different organs from N2cKO and WT mouse were sorted and the expression of CD36, whose upregulation by Notch2 signaling was implicated by the microarray, and CD14, which has a specific function in macrophages, was examined, using real time PCR and FACS analyses. [Results] Out of 20,000 genes that were covered by the microarray analysis, only 9 had reduced expression levels with N2cKO/WT ratio [Conclusions] MZB cells have been considered to play important roles at the border of the acquired and innate immunity. The data presented here support this paradigm, and further suggest that Notch2 signaling is crucial for the transcriptional regulation of genes being related to the innate immune function in MZB cells.