B Cell Depletion Inhibits Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice

Abstract

All NOD.H‐2h4 wild type (WT) mice given NaI water develop SAT, but B cell‐deficient (B−/−) mice are resistant. B cells presumably function as APC for activation of CD4+ T cells. B −/− mice develop SAT comparable to WT mice after transient depletion of T reg, suggesting T reg are preferentially activated if autoantigen is presented by non‐B cells. Anti‐CD20 or isotype control was given to young (1–2 wk) or adult (7 wk) WT mice; all mice were given NaI water at 8 wk, and SAT was evaluated 8 wk later. WT mice given anti‐CD20 at 1 and 2 wk of age developed minimal SAT, although B cells had repopulated by 6–8 wk of age. Transient depletion of T reg during B cell depletion reversed the effects of anti‐CD20, and all mice developed SAT. SAT was also inhibited in adult mice given anti‐CD20 if B cell depletion in blood was maintained for 8 wk. Transient B cell depletion of adult mice did not inhibit SAT development. Anti‐CD20 depleted most circulating B cells, but only 60–80% of splenic B cells in adults. Most follicular B cells were depleted, but marginal zone B cells were resistant. The results suggest that in the absence of B cells, other APC activate T reg. This may be one mechanism by which B cell depletion inhibits autoimmune disease. The effects of B cell depletion and the underlying mechanisms may differ depending on when anti‐CD20 is administered. (Supported by Arthritis Natl. Res. Fdn). Anti‐CD20 was provided by Drs. M. Kehry and R. Dunn, Biogen, Idec.

Fcγ Receptor Dependency of Agonistic CD40 Antibody in Lymphoma Therapy Can Be Overcome through Antibody Multimerization

“…These isotype-dependent therapeutic effects were specific to anti-CD40 rather than the BCL 1 model itself, as anti-CD20 (18B12) therapy demonstrated the opposite, classical, activatory FcgR-and mIgG2a mAb-dependent profile demonstrated in other models (Fig. 1H and data not shown) (13,16,24,26). It is notable that to produce a therapeutic effect in the BCL 1 model using direct targeting mAb such as anti-CD20 or anti-idiotype (data not shown), it is necessary to treat the mice at a very early stage (days 1-4) when the tumor burden is minimal and with large quantities of mAb (typically 200-250 ug).…”

“…Anti-mouse FcgRIIB (AT130-2) was produced in-house (23). Anti-mouse CD20 (18B12) mAb isotypes have been previously described (24). Endotoxin-free OVA (endoOVA) was from Profos (Regensburg, Germany).…”

Conventional B2 B Cell Depletion Ameliorates whereas Its Adoptive Transfer Aggravates Atherosclerosis

“…Based on the observations with B cell-depletion therapy, we revisited the role of B cells in atherosclerosis by depleting B lymphocytes using a mAb to mouse CD20 that has ameliorated murine thyroidits (13), lupus (14), and arthritis (15). We found that B cell depletion prevented the development and progression of atherosclerosis.…”

“…The protective role of B cells in atherosclerosis has stimulated interest in developing a protective vaccine for atherosclerosis, targeted toward harnessing the protective B cell-derived IgM response to oxidized LDL (8). B cell depletion mediated by mAb to CD20 remits a wide variety of inflammatory diseases in humans (9)(10)(11)(12) and mice (13)(14)(15)(16). In humans, rituximab, a chimeric Ab to human CD20, has been approved for treating intractable rheumatoid arthritis, although its value for other inflammatory diseases, such as systemic lupus erythematosus (10,11) and multiple sclerosis (12), is currently being assessed.…”

Transition of thyroid autoantibodies by rituximab treatment for thyroid MALT lymphoma

“…Accumulation of these cases is necessary to clarify whether the decreased in thyroid autoantibody levels by repeated rituximab monotherapy is associated with the improvement of disease state derived from Hashimoto's thyroiditis. resulted in diminished B lymphocyte and T lymphocyte infiltration of the thyroid, thereby inhibiting the development of spontaneous autoimmune thyroiditis [23]. In our present cases, thyroid autoantibody levels decreased after rituximab monotherapy.…”