Tissue healing is a delicate process that involves the interaction of several cellular elements and inflammatory chemical mediators. In this context, cytokines and cells of the immune response are part of a refined and intertwined mesh, and the rupture of any of the edges of this game of rods interferes negatively with the healing process (Fitzpatrick et al., 2019).

Oral ulcers are an essential tool for studying wound healing in mucous membranes since their repair is faster than skin ulcers, and as it is associated with pain and discomfort, the impact of delayed healing negatively interferes with food intake leading to worsening quality of life and weight reduction (Alkhateb et al., 2013).

After trauma and rupture of the epithelium, neutrophils migrate to the ulcer site to phagocytize microorganisms avoiding secondary infection initiating the acute phase of inflammation. Subsequently, macrophages are activated, and monocytes are recruited to complete the role not performed by neutrophils, as their survival is very short. In this moment, chronic inflation overlaps acute inflammation and subsequently the healing phase begins. After the polarization of macrophages from M1 to an M2 phenotype, the inflammatory profile changes, and lymphocytes are recruited and begin to produce anti-inflammatory cytokines and growth factors, consolidating the beginning of the wound repair phase. However, B lymphocytes are a cellular element little studied in this process (Liu et al., 2021a, Liu et al., 2021b).

B-lymphocytes are produced in the bone marrow and circulate in the bloodstream in a virgin state until exposed to antigens, mature into plasma cells, and start producing antibodies. In tissue healing, its role involves the production of cytokines and growth factors that modify the cellular profile of CD4 T lymphocytes (TCD4) from T-helper 1 (Th1) to T-helper 2 (Th2) (Xing et al., 2020). Therefore, blocking this cell can prolong the M1 phase of macrophages and the Th1 phase of TCD4 lymphocytes delaying wound repair, and in this context, drugs with potent anti-B lymphocyte properties can severely interfere with this process (Leshem et al., 2013), because LTCD4 activate B lymphocytes via CD40L-CD40 binding through signaling cascades of the Tumor Necrosis Factor alpha (TNF-α) superfamily, culminating in cell proliferation of B lymphocytes, production of pro-inflammatory cytokines and antibodies (Tang et al., 2021).

Rituximab (RTX) is an anti-CD20 monoclonal antibody that binds with very high affinity to CD20 molecules on the surface of B lymphocytes leading to caspase activation and cell death. It has been used since the 1990 s to treat B-lymphocyte leukemias and has recently gained approval for some autoimmune diseases such as rheumatoid arthritis resistant to anti- TNF-α agents (Bergantini et al., 2020, Salles et al., 2017).

Since the chronic use of RTX leads to intense immunosuppression and the blockade of inflammatory cascades at various levels is crucial for the reduction of healing of oral traumatic ulcers and in cutaneous ulcers RTX leads to delay wound healing (Selman et al., 2017), this study aims to analyze the impact of the use of RTX, an anti-CD20 monoclonal antibody, on wound healing in an experimental model of oral traumatic (OTU) ulcers in rats.