To examine the effect of IgG4-RD on early B cell activation in naive (CD27-) and memory B cells (CD27 + ), we used total internal reflection fluorescence microscopy (TIRFm) to examine BCR aggregation and B cell spreading following activation by membrane-tethered antigens (mAg) (Fig. S2A). Here, CD27 is linked to immunoglobulin G4-related sclerosing disease.