CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice.
BOB.1/OBF.1 (also called OCA-B), a B lymphocyte-specific transcriptional coactivator, is recruited to octamer-containing promoters by interacting with the Oct-1 or Oct-2 proteins. BOB.1/OBF.1-deficient mice show impaired secondary immunoglobulin isotype secretion and complete absence of germinal centers. Furthermore, numbers of splenic B cells are reduced due to a developmental block at the transitional B cell stage in the bone marrow. We found that surface expression of CD22 is selectively increased on B lineage cells in the bone marrow of BOB.1/OBF.1-deficient mice. CD22 is known as a negative regulator of B cell receptor signaling. We therefore investigated whether defects in B cell development in the BOB.1/OBF.1-deficient mice might be due to CD22 up-regulation. Mice were generated lacking both genes. In BOB.1/OBF.1xCD22 double-deficient mice, numbers of transitional B cells in the bone marrow were normal. Consequently, double-deficient mice also had normal B to T cell ratios in the spleen. We show that BOB.1/OBF.1(-/-) B cells were incapable to induce BCR-triggered Ca(2+) mobilization. This Ca(2+)-signalling defect was restored in BOB.1/OBF.1xCD22 double-deficient B cells. Nevertheless, double-deficient animals were unable to mount humoral immune responses and to form germinal centers. Finally, we demonstrate that CD22(-/-) splenic B cells proliferate independently of BOB.1/OBF.1 upon stimulation with LPS. These studies suggest that the B cell differentiation defect observed in BOB.1/OBF.1(-/-) mice is BCR-signal dependent. However, the impairment in germinal center formation is caused by a different mechanism.
Samardzic
Tatjana
T
Department of Physiological Chemistry, Ulm University, Germany.
Gerlach
Judith
J
Muller
Kerstin
K
Marinkovic
Dragan
D
Hess
Jochen
J
Nitschke
Lars
L
Wirth
Thomas
T
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology; D020013:Calcium Signaling; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D019070:Cell Lineage; D003433:Crosses, Genetic; D037102:Lectins / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D051918:Sialic Acid Binding Ig-like Lectin 2; D013154:Spleen / Q000166:cytology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D037102:Lectins; D008070:Lipopolysaccharides; C490424:Pou2af1 protein, mouse; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D015534:Trans-Activators