Fig. 4: IgM protects against severe placental sequestration.

a A low resolution map of IgM-VAR2CSA complex shows the bending of Cµ1-Cµ2 domains of IgM around VAR2CSA. The map is fitted with IgM-green, VAR2CSA domains; DBL1x-brown, ID2- red, DBL3x-cyan, DBL4ε-beige, ID3-magenta DBL5ε-blue, DBL6ε-yellow. Arrow and indigo color represents CSA binding pocket in the DBL2x domain. b FACS analysis using anti-VAR2CSA antibody on CS2 cultured in NHI-plasma (purple), Albumax (blue). CS2 cultured in Albumax was supplemented with 100 nM (red) and 1000 nM (green) IgM. c The box-whisker plot of the bound CS2 IEs on CSA in NHI-plasma (green), albumax (white), albumax+IgM (10 nM, light green), albumax+IgM (100 nM, green) and albumax+IgM (1000 nm, green) were counted and plotted as number of IEs bound/field. n = 3 performed in duplicates and 5 fields were counted per spot and represented as a point in the plot, cross (x) represents the mean, line crossing the box plot is the median, lowest and highest whisker represents minimum and maximum data point, whereas lower bound of the box represents Quartile 1 and upper bound of the box represents Quartile 3, dot outside the whisker are outliers (original values are available in source data). P values were calculated using paired t-test, ***P < 0.001, *P < 0.0517. d Atomic model (left) depicting the angle between chain A and chain L separated by J chain (bottom). green - IgM, purple-J chain, orange - N-terminus of VAR2CSA, blue - C-terminus of VAR2CSA e Schematic diagram of possible positions of C-termini of VAR2CSA in complex with IgM on IE surface where third option fulfills the distance and orientation criteria of (d). The surface rendered composite model of IgM-VAR2CSA complex represented on IE surface along with the right panel shows the schematics of presentation of VAR2CSA in absence and presence of IgM. f A hypothetical model for placental sequestration of IEs in presence and absence of IgM, which requires in vivo demonstration. In the presence of IgM, binding of VAR2CSA expressing IEs to CSPG (lime green) is compromised leading to lower sequestration. Panel 4 f was made using BioRender.