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Publication : Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory.

First Author  Chaplin JW Year  2013
Journal  J Exp Med Volume  210
Issue  10 Pages  2135-46
PubMed ID  24019553 Mgi Jnum  J:204086
Mgi Id  MGI:5529571 Doi  10.1084/jem.20130188
Citation  Chaplin JW, et al. (2013) Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory. J Exp Med 210(10):2135-46
abstractText  Antigen (Ag) targeting is an efficient way to induce immune responses. Ag is usually coupled to an antibody (Ab) specific for a receptor expressed on dendritic cells (DCs), and then the Ag-anti-receptor is inoculated with an adjuvant. Here we report that targeting Ag to a receptor expressed on both B cells and DCs, the TLR orphan receptor CD180, in the absence of adjuvant rapidly induced IgG responses that were stronger than those induced by Ag in alum. Ag conjugated to anti-CD180 (Ag-alphaCD180) induced affinity maturation and Ab responses that were partially T cell independent, as Ag-specific IgGs were generated in CD40- and T cell-deficient mice. After preimmunization with Ag-alphaCD180 and boosting with soluble Ag, both WT and CD40 knockout (KO) mice rapidly produced Ag-specific IgG-forming cells, demonstrating that Ag-anti-CD180 induces immunological memory. The potent adjuvant effect of Ag-alphaCD180 required Ag to be coupled to anti-CD180 and the responsive B cells to express both CD180 and an Ag-specific B cell receptor. Surprisingly, CD180 Ag targeting also induced IgG Abs in BAFF-R KO mice lacking mature B cells and in mice deficient in interferon signaling. Targeting Ag to CD180 may be useful for therapeutic vaccination and for vaccinating the immune compromised.
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