B-Cell suppression in adult mice injected with anti-delta followed by anti-mu mAb.
Cross-linking of surface IgM or IgD B-cell receptors (BCR) with appropriate anti-Ig antibodies induces IgM(high) or IgD(high) B-cell depletion, respectively. The aim of this paper is to analyze how injections of anti-delta followed by anti-mu monoclonal antibodies (mAb) can deplete and suppress B cells and then induce T-independent type 2 antigen tolerance in adult mice even after treatment is stopped. The experimental protocol consisted of three daily injections of anti-delta mAb followed by repeated injections of anti-mu mAb. It shows that a sequential injection of anti-delta and anti-mu mAb induces B-cell depletion and T-independent type 2 response downregulation. Morever, the T-dependent response is maintained, except for the IgG3 isotype. After clearance of the anti-delta mAb from the circulation, B cells reappear as an IgD(+) IgM(-) B-cell population in the bone marrow (BM) and spleen. The origin of IgD(+) IgM(-) cells was studied in scid mouse transfer models. We show that IgD(+) IgM(-) B cells are not mature cells reexpressing sIgD but BM-derived cells that require a T-cell presence to be developed. The lack of sIgM expression by posttranscriptional regulation and the need of T-cell help for escaping anti-mu negative selection suggest strongly that this population had properties similar to those of anergized B cells. These results support the potential use of sequential injections of anti-delta and anti-mu in the prevention of xenograft rejection.
Chentoufi
A A
AA
Experimental Immunology Unit, University of Louvain, Brussels, Belgium. chentoufiaziz@hotmail.com
Nizet
Y
Y
Havaux
X
X
Nisol
F
F
Bazin
H
H
Latinne
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000955:Antigens, T-Independent / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004140:Dinitrophenols / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000955:Antigens, T-Independent; D004140:Dinitrophenols; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; C045521:dinitrophenol-ovalbumin; C050855:immunoglobulin D receptor; C035311:immunoglobulin M receptor; D010047:Ovalbumin