CD22 regulates B lymphocyte function in vivo through both ligand-dependent and ligand-independent mechanisms.
The interaction of CD22 with alpha2,6-linked sialic acid ligands has been widely proposed to regulate B lymphocyte function and migration. Here, we generated gene-targeted mice that express mutant CD22 molecules that do not interact with these ligands. CD22 ligand binding regulated the expression of cell surface CD22, immunoglobulin M and major histocompatibility complex class II on mature B cells, maintenance of the marginal zone B cell population, optimal B cell antigen receptor-induced proliferation, and B cell turnover rates. However, CD22 negative regulation of calcium mobilization after B cell antigen receptor ligation, CD22 phosphorylation, recruitment of SHP-1 to CD22 and B cell migration did not require CD22 ligand engagement. These observations resolve longstanding questions regarding the physiological importance of CD22 ligand binding in the regulation of B cell function in vivo.
Poe
Jonathan C
JC
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Fujimoto
Yoko
Y
Hasegawa
Minoru
M
Haas
Karen M
KM
Miller
Ann S
AS
Sanford
Isaac G
IG
Bock
Cheryl B
CB
Fujimoto
Manabu
M
Tedder
Thomas F
TF
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement; D037102:Lectins / Q000502:physiology*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D051918:Sialic Acid Binding Ig-like Lectin 2
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D037102:Lectins; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D019158:N-Acetylneuraminic Acid