Phenotypic expansion of POGZ-related intellectual disability syndrome (White-Sutton syndrome).

White-Sutton syndrome (WHSUS) is a recently-identified genetic disorder resulting from de novo heterozygous pathogenic variants in POGZ. Thus far, over 50 individuals have been reported worldwide, however phenotypic characterization and data regarding the natural history are still incomplete. Here we report the clinical features of 22 individuals with 21 unique loss of function POGZ variants.

Proteolysis increases the Fc-mediated binding of murine IgG2b to human EBV-transformed B cells, but decreases the expression of Fc gamma RII and Fc epsilon RII.

We have previously described a polymorphic human Fc receptor for murine IgG2b (mIgG2b). This receptor was defined by the binding of (complexed) mIgG2b to monocytes and Epstein-Barr virus (EBV)-transformed B cells. Three per cent of normal individuals were high responders with respect to mIgG2b (mIgG2b-HR), whereas the other individuals were low responders for mIgG2b (mIgG2b-LR).

The human Fc receptor for mouse IgG2b on monocytes and EBV-B cells is functionally inhibited by anti-HLA class II antibodies.

We have recently described a polymorphic Fc receptor for murine IgG2b (mIgG2b), present on human monocytes and EBV-transformed B lymphocytes. The present study shows that anti-HLA class II monoclonal antibody (MoAb) completely inhibits both the (Fc receptor-dependent) T-cell proliferation, induced by mIgG2b anti-CD3 MoAb, and rosetting with mIgG2b-sensitized erythrocytes. This inhibition is also observed with F(ab')2 fragments of anti-HLA class II MoAb, and is therefore not Fc mediated.

Removal of monocytes from cell suspensions with anti-CD14 antibody and carbonyl-iron, using Fc gamma R-dependent accessory function as a sensitive measure of monocyte presence.

Human (Fc gamma RI-positive) monocytes are required as accessory cells when T cell proliferation is induced by murine IgG2a anti-CD3 monoclonal antibodies (mAbs). This T cell proliferation assay provides a sensitive method for detecting the presence of monocytes (less than 1% of monocytes can be detected), and we have used it to monitor the effectiveness of different procedures for the removal of monocytes from peripheral blood mononuclear cells. Counterflow centrifugation, phagocytosis of carbonyl-iron, adherence to plastic, monocyte depletion with magnetic beads (Dynabeads M450), and panning with anti-CD14 antibodies each strongly reduced the number of monocytes.

A polymorphic Fc receptor for mouse IgG2b on human B cells and monocytes.

With respect to murine (m)IgG1 anti-CD3 monoclonal antibody (mAb), a polymorphic mitogenic response of peripheral blood mononuclear cells (PBMC) has been described which is caused by polymorphism of monocyte Fc gamma RII, and which defines high responders to mIgG1 (mIgG1-HR, approximately 70% of normal individuals) and low responders (mIgG1-LR). PBMC also exhibit a polymorphic mitogenic response to mIgG2b anti-CD3 mAb. In the present study 18 out of 550 individuals (3%) were mIgG2b-HR.