CD19, CD21, and CD22: multifaceted response regulators of B lymphocyte signal transduction.
B lymphocyte development and function depend upon the activity of intrinsic and B cell antigen receptor (BCR)-induced signals. These signals are interpreted, amplified, fine-tuned, or suppressed through the precise actions of specialized cell surface coreceptors, or "response regulators," that inform B cells of their extracellular environment. Important cell surface response regulators include the CD19/CD21 complex, CD22, and CD72. CD19 establishes a novel Src-family protein tyrosine kinase (PTK) amplification loop that regulates basal signaling thresholds and intensifies Src-family PTK activation following BCR ligation. In turn, CD22 limits the intensity of CD19-dependent, BCR-generated signals through the recruitment of potent phosphotyrosine and phosphoinositide phosphatases. Herein we discuss our current understanding of how CD19/CD21 and CD22 govern the emergence and intensity of BCR-mediated signals, and how alterations in these tightly controlled regulatory activities contribute to autoimmunity in mice and humans.
Poe
J C
JC
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Hasegawa
M
M
Tedder
T F
TF
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018941:Antigens, CD19 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules; D006801:Humans; D037102:Lectins; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D017464:Receptors, Complement 3d; D051918:Sialic Acid Binding Ig-like Lectin 2; D019061:src-Family Kinases