a, Representative images of myelin labelled with a pH-sensitive fluorescent dye (CypHer5E, white), a constitutively fluorescent dye (AF555, red) and stained for IBA1 (green). The majority of AF555 overlapping with IBA1 is also positive for CypHer5E, indicating localization to an acidified compartment. Scale bars, 100 μm. b, 3D reconstruction of a microglial cell (IBA1, green) with ingested myelin (CypHer5E and AF555, white and red, yellow arrow) near un-ingested myelin (AF555, red, white arrow). Scale bar, 5 μm. c, Microgliosis, as assessed by percentage of IBA1+ area at the injection site, was not altered by CD22 blockade (n = 8, paired two-sided t-test). d, Representative images of myelin (red) overlaid with the myeloid marker IBA1 (green) at the injection site of IgG (left) or PBS (middle) treated hemispheres of the same aged brain, or an image of a stab wound control (not injected with myelin). Scale bars, 100 μm. e, Microgliosis, as assessed by percentage of IBA1+ area at the injection site, was not altered by IgG compared to the stab wound control (n = 2, paired two-sided t-test). f, Clearance of myelin debris in the IgG (black) or PBS (blue) treated hemispheres assessed 48 h post-injection (n = 4, paired two-sided t-test). g, Representative images of IBA1 (grey), a macrophage marker, and TMEM119 (magenta), a microglia-specific marker, at the injection site in IgG (left) or anti-CD22 (right) treated hemispheres of the same aged brain. Scale bars, 100 μm. h, Percentage of IBA1+ phagocytes expressing TMEM119 at the injection site (n = 4, paired two-sided t-test). i, Clearance of myelin debris in young (2.5-month-old) wild-type (black) or Cd22−/− (blue) mice was assessed 48 h after injection (n = 4, two-sided t-test; mean ± s.e.m.). j, Representative images of total Aβ (white), thioflavin S+ fibrillar Aβ (green) and IBA1 (red) in transgenic mice expressing human APP with Swedish and London familial AD mutations (left) or wild-type mice injected with Aβ oligomers 48 h before analysis (right). k, Representative images of Aβ (red, left column) and Aβ overlaid with the myeloid marker IBA1 (green, right column) at the injection site (±2 mm lateral, 0 mm A–P, −1.5mm D–V, relative to bregma) of IgG (top row) or anti-CD22 (bottom row) treated hemispheres of the same aged brain. Scale bars, 100 μm. l, Microgliosis, as assessed by percentage of IBA1+ area at the Aβ oligomer injection site, was not altered by CD22 blockade (n = 8, paired two-sided t-test). m, Representative images of α-synuclein and IBA1 at the injection site in IgG and anti-CD22 treated mice. Scale bars, 100 μm. n, Clearance of α-synuclein fibrils in the IgG (black) or anti-CD22 (green) treated hemispheres assessed 48 h post-injection (n = 7, *P < 0.05, paired two-sided t-test). o, Microgliosis, as assessed by percentage of IBA1+ area at the α-synuclein fibril injection site, was not altered by CD22 blockade (n = 7, paired two-sided t-test). All data were replicated in at least two independent experiments. Source data