Spontaneous follicular exclusion of SHP1-deficient B cells is conditional on the presence of competitor wild-type B cells.
Engagement of antigen receptors on mature B lymphocytes is known to block cell entry into lymphoid follicles and promote accumulation in T cell zones, yet the molecular basis for this change in cell distribution is not understood. Previous studies have shown that follicular exclusion requires a threshold level of antigen receptor engagement combined with occupancy of follicles by B cells without equivalent receptor engagement. The possibility has been raised that follicular composition affects B cell positioning by altering the amount of available antigen and the degree of receptor occupancy. Here we show that follicular composition affects migration of mature B cells under conditions that are independent of antigen receptor occupancy. B cells deficient in the negative regulatory protein tyrosine phosphatase, SHP1, which have elevated intracellular signaling by the B cell receptor, are shown to accumulate in the T zone in the absence of their specific antigen. Follicular exclusion of SHP1-deficient B cells was found to be conditional on the presence of excess B cells that lack elevated intracellular signaling, and was not due to a failure of SHP-1-deficient cells to mature and express the follicle-homing chemokine receptor Burkitt's lymphoma receptor 1. These findings strongly suggest that signals that are negatively regulated by SHP1 promote B cell localization in T cell zones by reducing competitiveness for follicular entry, and provide further evidence that follicular composition influences the positioning of antigen-engaged B cells.
Schmidt
K N
KN
Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143, USA.
Hsu
C W
CW
Griffin
C T
CT
Goodnow
C C
CC
Cyster
J G
JG
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D015815:Cell Adhesion Molecules; D019204:GTP-Binding Proteins / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000502:physiology*; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000032:analysis; D051918:Sialic Acid Binding Ig-like Lectin 2
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C513179:CXCR5 protein, mouse; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D051918:Sialic Acid Binding Ig-like Lectin 2; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D019204:GTP-Binding Proteins