Differential effects of injections of anti-mu and anti-delta monoclonal antibodies on B-cell populations in adult mice: regulation of xenoreactive natural antibody-producing cells.
BACKGROUND
The depletion of differential B cell and xenoreactive natural antibodies (XNA) by anti-delta and anti-mu injections was analyzed in adult mice. Sequential treatment with anti-delta and then anti-mu induces a complete depletion of B cells and XNA and represents a potential approach to induce xenograft tolerance.


METHODS
Adult mice were injected with anti-mu, anti-delta, anti-delta then anti-mu, or control isotype monoclonal antibodies from day 0 to day 14. The different B-cell populations were analyzed by FACS and immunohistology. Ig production was tested by ELISA. XNA were analyzed by FACS.


RESULTS
Anti-mu injections induced a depletion of IgMhigh, immature B cells, marginal zone B cells, and B1 cells and an increase of IgG-XNA production. Anti-delta injections induced mature conventional IgDhigh B-cell depletion and increased IgM-XNA production. Interestingly, sequential injections of anti-delta then anti-mu induced a depletion of immature B cells, mature B cells (MZ, B2, and B1), and XNA.


CONCLUSIONS
These results demonstrate that mature B-cell depletion in adult mice can be obtained by mAb injections and depends on the surface immunoglobulin cross-linking threshold. Indeed, anti-mu mAb depleted IgMhigh B cells (MZ and B1) and anti-delta, IgDhigh B cells (B2). The differential B-cell suppression shows that conventional B cells are responsible in the IgG-XNA production and MZ and B1 cells in the IgM-XNA production. Sequential repeated injections of anti-delta then anti-mu mAb depleted all B-cell populations and suppressed the whole XNA production.
Chentoufi
A A
AA
Experimental Immunology Unit, School of Medicine, University of Louvain, Brussels, Belgium.
Nizet
Y
Y
Havaux
X
X
De La Parra
B
B
Cormont
F
F
Hermans
D
D
Bazin
H
H
Latinne
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000955:Antigens, T-Independent / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002452:Cell Count / Q000187:drug effects; D005260:Female; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007138:Immunoglobulin delta-Chains / Q000276:immunology*; D007148:Immunoglobulin mu-Chains / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D013552:Swine
D000911:Antibodies, Monoclonal; D000955:Antigens, T-Independent; D007132:Immunoglobulin Isotypes; D007138:Immunoglobulin delta-Chains; D007148:Immunoglobulin mu-Chains; D007136:Immunoglobulins