(A) New emigrant B cells from IRAK-4- and MyD88-deficient patients
have an increased proportion of autoreactive lambda clones compared to
controls and UNC-93B-deficient patients. Histograms represent means
± s.e.m. of proportion of κ (black bars) and
λ (open bars) clones that are autoreactive (polyreactive and
HEp-2-reactive combined).
(B) Autoreactive IRAK-4- and MyD88-deficient new emigrant B cells
display a lambda repertoire suggesting defective receptor editing. Pie
charts show the proportion of the different Jλ genes in
non-autoreactive and autoreactive new emigrant B cells from healthy controls
(top panel) or IRAK-4- and MyD88-deficient patients (bottom panel), with the
number of analyzed sequences indicated in the centers.
(C) Most ANA and all kinetoplast-reactive B cells from IRAK-4 and
MyD88-deficient patients express kappa chains. Histograms represent means
± s.e.m. of proportion of κ (black bars) and
λ (open bars) clones that are anti-nuclear (top panel) and
anti-kinetoplast (bottom panel).
(D) The ANA expressed by IRAK-4- and MyD88-deficient new emigrant B
cells do not show any bias towards downstream Jκ3,4,5 usage
compared to the non-ANA clones. Pie charts show the proportion of the
different Jκ genes, with the number of analyzed sequences
indicated in the centers.
(E) The ANA expressed in IRAK-4-and MyD88-deficient new emigrant B
cells do not show any bias towards upstream Vκ gene usage
compared to the non-ANA clones. The Vκ locus is shown below
clustered into 4 clans of Vκ gene segments. Histograms represent
the proportion of genes of each Vκ group for ANA (black bars)
and non-ANA (open bars) expressed by new emigrant B cells from IRAK-4- and
MyD88-deficient patients.