SAP is required for Th cell function and for immunity to influenza.
Ab is a crucial component of protective immunity to infection, but Ab responses do not proceed normally when defects occur in a protein called signaling lymphocytic activation molecule-associated protein (SAP). To explain this Ab defect, we analyzed B cell and plasma cell responses under conditions of SAP deficiency. Our results demonstrate that SAP-deficient (SAP knockout (KO)) mice have a profound CD4 T cell-intrinsic defect in generating Ag-specific plasma cells following challenge with model Ags or influenza virus, resulting in low Ag-specific Ab titers. We also show that SAP is required in CD4 T cells for normal division and expansion of B cells. These B cell and plasma cell defects were observed during the expansion phase of the primary immune response, indicating early defects in Th cell activity. In fact, additional experiments revealed a nearly complete lack of T cell help for B cells in SAP KO mice. Our work suggests that the ability of SAP to promote T-dependent humoral immune responses is important for antiviral immunity because mice lacking SAP are unable to prevent high dose secondary influenza infection, and because passive transfer of IgG in immune serum from wild-type, but not SAP KO mice can protect mice from an otherwise lethal influenza infection. Overall, our results demonstrate that SAP is required in CD4 T cells for their ability to help B cell responses and promote influenza-specific immunity.
Kamperschroer
Cris
C
Trudeau Institute, Saranac Lake, NY 12983, USA.
Dibble
John P
JP
Meents
Dana L
DL
Schwartzberg
Pamela L
PL
Swain
Susan L
SL
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D010950:Plasma Cells; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D047908:Intracellular Signaling Peptides and Proteins; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein