CD47 Blockade Leads to Chemokine-Dependent Monocyte Infiltration and Loss of B Cells from the Splenic Marginal Zone

CD47 is an important innate immune checkpoint through its interaction with its inhibitory receptor on macrophages, signal-regulatory protein alpha (SIRP alpha). Therapeutic blockade of CD47-SIRP alpha interactions is a promising immuno-oncology treatment that promotes clearance of cancer cells. However, CD47-SIRP alpha interactions also maintain homeostatic lymphocyte levels. In this study, we report that the mouse splenic marginal zone B cell population is dependent on intact CD47-SIRP alpha interactions and blockade of CD47 leads to the loss of these cells. This depletion is accompanied by elevated levels of monocyte-recruiting chemokines CCL2 and CCL7 and infiltration of CCR2(+)Ly6C(hi) monocytes into the mouse spleen. In the absence of CCR2 signaling, there is no infiltration and reduced marginal zone B cell depletion. These data suggest that CD47 blockade leads to clearance of splenic marginal zone B cells.

Automated summary

CD47 blockade is a promising immuno-oncology treatment that promotes clearance of cancer cells, but it also leads to depletion of splenic marginal zone B cells, which is dependent on intact CD47-SIRP alpha interactions.