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J Neuroimmune Pharmacol. 2019 Dec;14(4):709-719. doi: 10.1007/s11481-019-09872-z. Epub 2019 Aug 21.

Low-Dose Subcutaneous Anti-CD20 Treatment Depletes Disease Relevant B Cell Subsets and Attenuates Neuroinflammation.

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Autoimmunity, Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Neuroscience Development Unit, Novartis Pharma AG, Basel, Switzerland.
Autoimmunity, Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA.


To explore the B cell depleting capacity of a low-dose (20 μg) subcutaneous mouse anti-CD20 antibody treatment on disease-relevant B cell populations within lymph nodes and the spleen. B cell depleting capacity was explored in healthy female C57BL/6 and BALB/c mice; following immune activation in two different mouse models: trinitrophenylated lipopolysaccharide model (thymus-independent response) and dinitrophenyl-keyhole limpet hemocyanin model (thymus-dependent response); and in a chronic neuroinflammation experimental autoimmune encephalomyelitis model. CD20 protein expression on B cell subpopulations was also studied. The subcutaneous anti-CD20 regimen resulted in rapid depletion of B cells in blood, lymph nodes and spleen. Low-dose subcutaneous treatment did not reduce antigen-specific immunoglobulin M and immunoglobulin G titers in all subgroups, and relatively spared splenic marginal zone (MZ) B cells in both T cell dependent and T cell independent B cell immunization models. Analysis of immune compartments during anti-CD20-modulated autoimmune neuroinflammation showed that the maximal B cell depletion was achieved within 2 days of treatment and was highest in the lymph node. Regardless of the tissues analyzed, low-dose subcutaneous treatment was characterized by rapid B cell repletion following treatment cessation. CD20 protein expression was consistent on all B cell subsets in blood, and was more pronounced in germinal center B cells of lymph nodes and MZ B-cells of the spleen. Low-dose subcutaneous anti-CD20 therapy effectively depleted B cells within lymphatic tissues and reduced the severity of neuroinflammation. These data suggest that subcutaneous anti-CD20 therapies can effectively target disease-relevant B cell populations, have shorter repletion kinetics and maintain vaccination responses, thereby achieving autoimmune amelioration without severely impacting immune surveillance functions. Graphical Abstract *p < 0.05; **p < 0.01. CD, cluster of differentiation; DNP-KLH, dinitrophenyl-keyhole limpet hemocyanin; EC50, concentration of a drug that gives half-maximal response; Ig, immunoglobulin; MZ, marginal zone; s.c., subcutaneous; SEM, standard error of mean; TNP-LPS, trinitrophenylatedlipopolysaccharide.


Anti-CD20 monoclonal antibody; Lymph node; Marginal zone B cells; Ofatumumab; Spleen; Subcutaneous


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