DOCK8 and MyD88 have been implicated in serologic memory. Here we report antibody responses were impaired and CD27+ memory B cells were severely reduced in DOCK8-deficient patients. Toll-like receptor 9 (TLR9)- but not CD40-driven B cell proliferation and immunoglobulin production were severely reduced in DOCK8-deficient B cells. In contrast, TLR9-driven expression of AICDA, CD23 and CD86, and activation of NF-κB, p38 and Rac1 were intact. DOCK8 associated constitutively with MyD88 and the tyrosine kinase Pyk2 in normal B cells. Following TLR9 ligation, DOCK8 became tyrosine phosphorylated by Pyk2, bound the Src family kinase Lyn and linked TLR9 to a Src-Syk-STAT3 cascade essential for TLR9-driven B cell proliferation and differentiation. Thus, DOCK8 functions as an adaptor in a TLR9-MyD88 signaling pathway in B cells.

In the original version of Figure 2B, two of the patient identifiers were incorrectly noted. OS-11 and OS-12 were listed twice. The second instances should have been labeled as CID-11 and CID-12, respectively. The correct figure panel is below.The authors regret the error.

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In the original version of Figure 2B, two of the patient identifiers were incorrectly noted. OS-11 and OS-12 were listed twice. The second instances should have been labeled as CID-11 and CID-12, respectively. The correct figure panel is below.The authors regret the error.