title: Activated mouse B cells lack expression of granzyme B.
abstract: Recently, it has been reported that human B cells express and secrete the cytotoxic protease granzyme B (GrB) after stimulation with IL-21 and BCR cross-linking. To date, there are few clues on the function of GrB in B cell biology. As experimental transgenic murine systems should provide insights into these issues, we assayed for GrB in C57BL/6 B cells using an extensive array of physiologically relevant stimuli but were unable to detect either GrB expression or its proteolytic activity, even when Ag-specific transgenic BCRs were engaged. Similar results were also obtained with B cells from DBA/2, CBA, or BALB/c mice. In vivo, infection with either influenza virus or murine γ-herpesvirus induced the expected expression of GrB in CTLs, but not in B cell populations. We also investigated a possible role of GrB on the humoral immune response to the model Ag 4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyanin, but GrB-deficient mice produced normal amounts of Ab with typical affinity maturation and a heightened secondary response, demonstrating conclusively the redundancy of GrB for Ab responses. Our results highlight the complex evolutionary differences that have shaped the immune systems of mice and humans. The physiological consequences of GrB expression in human B cells remain unclear, and the current study suggests that experimental mouse models will not be helpful in addressing this issue.
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Hagn
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
authors.forename: Vivien R
authors.initials: VR
authors.lastname: Sutton
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Thia
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Hawkins
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Trapani
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D018142:Gammaherpesvirinae; D053804:Granzymes / Q000276:immunology / Q000378:metabolism*; D006241:Haptens; D006433:Hemocyanins / Q000494:pharmacology; D006566:Herpesviridae Infections / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D007378:Interleukins / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009975:Orthomyxoviridae; D009976:Orthomyxoviridae Infections / Q000201:enzymology / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D000098546:Interleukin-21
chemical_list: C098951:4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyanin; D000914:Antibodies, Viral; D006241:Haptens; D007378:Interleukins; D011947:Receptors, Antigen, B-Cell; D006433:Hemocyanins; D053804:Granzymes; D000098546:Interleukin-21