IL-15 temporally reorients IL-10 biased B-1a cells toward IL-12 expression.
Interleukin (IL)-15 is known to strongly modulate T-cell function; however, its role in controlling mucosal immunity, including its ability to modulate B-1a cell activity, remains to be elucidated. Here, we show that IL-15 upregulates activation molecules and the costimulatory molecule CD80 on viable B-1a cells. Cell activation was accompanied by the depletion of sialic acid-binding immunoglobulin-like lectin (Siglec)-G, an inhibitor of cell activation that is present on B-1a cells. The IL-15 receptor CD122 was stimulated on B-1a cells by the cytokine showing its direct involvement in IL-15-mediated responses. IL-10 is responsible for the long term survival of B-1a cells in culture, which is initially promoted by IL-15. The upregulation of IL-10 was followed by the appearance of suppressor of cytokine signaling (SOCS)1 in the presence of IL-15 and the loss of IL-10. This resulted in the cells switching to IL-12 expression. This anti-inflammatory to pro-inflammatory shift in the B-1a cell character was independent of the cell-specific marker CD5, which remained highly expressed throughout the in vitro life of the cells. The presence of the immunosuppressive receptor programmed cell death (PD)-1 and its ligand PD-L2 were features of a predominantly IL-10 response. PD-1 and PD-L2 can mediate juxtacrine signaling. However, the abrogation of PD-1 and its ligand was observed when the cells expressed IL-12. This demonstrates an inverse relationship between the receptor and ligand and the pro-inflammatory cytokine. The induction of IgM and IgA, which can play pivotal roles in mucosal immunity, was promoted in the presence of IL-15. Collectively, the data implicate IL-15 as the master cytokine that induces B-1a cells to mount a mucosal immune response.
Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
Amlan
A
Kanti Ghosh
Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
Debolina
D
Sinha
Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
Subhadeep
S
Mukherjee
Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
Ratna
R
Biswas
Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
Tapas
T
Biswas
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D018928:Immunity, Mucosal / Q000502:physiology*; D007070:Immunoglobulin A / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology*; D037102:Lectins / Q000276:immunology; D051379:Mice; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000276:immunology
C556062:IL10 protein, mouse; D007070:Immunoglobulin A; D019409:Interleukin-15; D037102:Lectins; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D011947:Receptors, Antigen, B-Cell; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D016753:Interleukin-10; D018664:Interleukin-12