CD20 deficiency in humans results in impaired T cell–independent antibody responses

Abstract

CD20 was the first B cell differentiation antigen identified, and CD20-specific mAbs are commonly used for the treatment of B cell malignancies and autoantibody-mediated autoimmune diseases. Despite this the role of CD20 in human B cell physiology has remained elusive. We describe here a juvenile patient with CD20 deficiency due to a homozygous mutation in a splice junction of the CD20 gene (also known as MS4A1) that results in "cryptic" splicing and nonfunctional mRNA species. Analysis of this patient has led us to conclude that CD20 has a central role in the generation of T cell-independent (TI) antibody responses. Key evidence to support this conclusion was provided by the observation that although antigen-independent B cells developed normally in the absence of CD20 expression, antibody formation, particularly after vaccination with TI antigens, was strongly impaired in the patient. Consistent with this, TI antipolysaccharide B cell responses were severely impeded in CD20-deficient mice. Our study therefore identifies what we believe to be a novel type of humoral immunodeficiency caused by CD20 deficiency and characterized by normal development of antigenindependent B cells, along with a reduced capacity to mount proper antibody responses.

Synergistic activation by p38MAPK and glucocorticoid signaling mediates induction of M2‐like tumor‐associated macrophages expressing the novel CD20 homolog MS4A8A

“…CD20, for example, plays a central role in the generation of T cellindependent antibody responses. 32 As CD20 is present on the majority of B-cell lymphomas, a therapeutic antibody has been created, which is successfully used in the therapy of non-Hodgkin lymphomas.…”

CD20+T cells have a predominantly Tc1 effector memory phenotype and are expanded in the ascites of patients with ovarian cancer

“…In this respect, B cells from a juvenile patient with CD20 deficiency did not differ in basal calcium flux in response to treatment with IgG or IgM, but were defective in antibody production. 27 Further insight into the role of CD20 may help uncover whether CD20 has a function on CD20…”

B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele

“…2,3 In about 90% of patients diagnosed with agammaglobulinemia and about 75% of cases with a Hyper-IgM syndrome, the underlying genetic defect has been identified. 2 Whereas mutations have been described in patients diagnosed with CVID, [4][5][6][7][8][9][10][11][12] in over 90% of these patients no associated genetic defect has been found. In fact, in most CVID patients a complex genetic trade rather than a single affected gene is likely to contribute to development of the disease.…”