Mouse germinal center B cells with the xid mutation retain responsiveness to antimouse CD40 antibodies but diminish IL-5 responsiveness.
The germinal center (GC) develops in secondary lymphoid tissues in response to thymus-dependent (TD) antigens. To investigate the molecular mechanism of B cell differentiation in GC, we enriched GC B cells from spleen of TD antigen-immunized wild-type and X-linked immunodeficient (XID) mice, and examined the differentiation of GC B cells into antigen-specific IgG1 antibody-forming cells (AFC) in response to anti-CD40 mAb and cytokines. A significant proportion of freshly purified GC B cells expressed receptors for IL-4 and IL-5. Anti-CD40 mAb sustained the viability of GC B cells and IL-4 co-operated with anti-CD40 mAb for further enhancement of the cell viability. Anti-CD40 mAb and IL-4 were essential for inducing differentiation of GC B cells into antigen-specific IgG1-AFC and IL-5 efficiently enhanced their differentiation. GC B cells with the xid mutation responded for proliferation to CD40 ligation to a lesser extent and for the IgG1-AFC response to anti-CD40 mAb together with IL-4, but they showed impaired responsiveness to IL-5, regardless of enhanced expression of IL-5R in response to anti-CD40 mAb and IL-4. These results suggest that anti-CD40 mAb, IL-4 and IL-5 play a critical role in the differentiation of mouse GC B cells. The GC B cells from XID mice show a functional defect with respect to IL-5-mediated differentiation.
Baba
M
M
Department of Immunology, University of Tokyo, Japan.
Kikuchi
Y
Y
Mori
S
S
Kimoto
H
H
Inui
S
S
Sakaguchi
N
N
Inoue
J
J
Yamamoto
T
T
Takemori
T
T
Howard
M
M
Takatsu
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation; D002470:Cell Survival; D005260:Female; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D015848:Interleukin-5 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009154:Mutation; D010641:Phenotype; D018123:Receptors, Interleukin / Q000378:metabolism; D053649:Receptors, Interleukin-5; D014960:X Chromosome
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007074:Immunoglobulin G; D015848:Interleukin-5; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5