Whole-body autoradiography reveals that the Peptostreptococcus magnus immunoglobulin-binding domains of protein L preferentially target B lymphocytes in the spleen and lymph nodes in vivo.
Protein L is an immunoglobulin (Ig)-binding protein produced by the Gram-positive bacterium Peptostreptococcus magnus that interacts with the variable region of Ig kappa light chains. The Ig light chain-binding capacity of protein L gives it the potential to interact with cells expressing surface Ig such as B cells. The present study was performed to address the in vivo trafficking of protein L at both the organ and the cellular level. Using the powerful technique of whole-body autoradiography in a murine model system, we demonstrate specific targeting of protein L to secondary lymphoid tissues in whole-animal analysis. The observed targeting depends on the capacity to interact with murine Ig, as tissue targeting was not apparent in mice given protein H, an Ig-binding protein produced by Streptococcus pyogenes with affinity for human but not murine Ig. Tissue targeting data were combined with flow cytometry analysis, which demonstrated the capacity of protein L to target and activate B lymphocytes in vivo. B cells targeted by protein L had increased surface expression of CD86 and MHC-II, and protein L was present in vacuolar compartments of B cells. Protein L did not bind T cells or natural killer cells but had some capacity to target dendritic cells and macrophages. The data show that protein L preferentially targets secondary lymphoid organs, and activates and is internalized by B cells in vivo. Furthermore, the observed tissue and cell targeting properties require an affinity for murine Ig. These data support the potential use of this Ig-binding protein as a targeting approach to deliver agents to defined cell populations in vivo.
Smith
David
D
Section for Immunology, Department of Cell and Molecular Biology, Lund University, Lund, Sweden.
D'Argy
Roland
R
Nilsson
Mats
M
Yrlid
Ulf
U
de Jersey
James
J
Björck
Lars
L
Wick
Mary Jo
MJ
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D005434:Flow Cytometry; D007457:Iodine Radioisotopes / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010462:Peptostreptococcus / Q000378:metabolism / Q000472:pathogenicity; D013154:Spleen / Q000166:cytology / Q000276:immunology*
D001426:Bacterial Proteins; C055047:Ig L-binding protein, Peptostreptococcus; D007457:Iodine Radioisotopes