IL-4 promotes the migration of circulating B cells to the spleen and increases splenic B cell survival.
We report that IL-4 causes a redistribution of B cells and modestly increases B cell life span. Intravenous injection of a long-acting formulation of IL-4 induces increases in both spleen cell number and the percentage of splenic B cells. These effects are observed within 1 day of IL-4 administration and plateau after approximately 3 days if IL-4 treatment is continued. The increase in splenic B cell number is IL-4 dose dependent, CD4+ T cell independent, FcgammaRII/FcgammaRIII independent, and Stat6 independent. Decreases in the number of B cells in the blood and the percentage of mature B cells in the bone marrow, concomitant with the increase in splenic B cell number, suggest that redistribution of circulating B cells to the spleen is partially responsible for IL-4 induction of splenic B cell hyperplasia. Considerable reduction in the effect of 5 days of IL-4 treatment on splenic B cell number when B lymphopoiesis is blocked with anti-IL-7 mAb suggests that generation of new B cells is also involved in IL-4-induced splenic B cell hyperplasia. 5-Bromo-2'-deoxyuridine labeling experiments demonstrate that IL-4 modestly prolongs the life span of newly generated splenic B cells, and experiments that measure B cell HSA (CD24) expression as an indicator of B cell age suggest that IL-4 may also prolong the life span of mature splenic B cells. Thus, IL-4 increases splenic B cell number through two Stat6-independent effects: increased net migration of circulating B cells to the spleen and increased B cell life span. Both effects may promote Ab responses to a systemic Ag challenge.
Mori
M
M
Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Morris
S C
SC
Orekhova
T
T
Marinaro
M
M
Giannini
E
E
Finkelman
F D
FD
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D018985:Epitopes, B-Lymphocyte / Q000032:analysis; D005260:Female; D007275:Injections, Intravenous; D015847:Interleukin-4 / Q000008:administration & dosage / Q000494:pharmacology*; D015851:Interleukin-7 / Q000502:physiology; D007700:Kinetics; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000502:physiology; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology
D018985:Epitopes, B-Lymphocyte; D015851:Interleukin-7; D017452:Receptors, IgG; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4