B lymphocytes are central players in the immune response; canonically, they have been recognized as precursors of antibody-producing cells: plasma cells. Recent findings have shown that the role of B lymphocytes goes far beyond the production of antibodies. There are different subtypes of B lymphocytes with different participations in innate and adaptive responses that include the recognition of the antigen, its processing, and its presentation to T lymphocytes, as well as the production of cytokines that impact and modulate the response toward the pathogen. Traditionally, it has been considered that B lymphocytes do not have phagocytic abilities that allow them to internalize, to process, or even to be infected by bacterial pathogens. The new information has shown that B lymphocytes can be readily infected by bacterial pathogens like Salmonella, Francisella, Moraxella, and Mycobacterium, among others, and respond to those infections. Some of the recent advances on these topics will be presented in this chapter.use of radioactive labels, it was demonstrated that circulating lymphocytes stimulated with antigen were the precursors of antibody-producing cells [15,16], and by the year 1969, the two populations of lymphocytes were identified as T lymphocytes for those thymic-dependent, and those thymic-independent (bursa-equivalent) were referred as B lymphocytes [17].Afterward, it was established in non-avian experimental models that a cooperative response of both lymphocyte species (T and B) was necessary for specific antibody production [18];these observations prompted a large number of studies that recognized the complexity of T-B cooperation, resulting in specific responses to the antigen, including the production of specific high-affinity antibodies [19]. B lymphocytes: a bridge between innate and adaptive immune responsesIt is now known that there are several types of B lymphocytes [20] and that B2 lymphocytes produce specific antibodies during the adaptive response [21]. On the other side, there are also natural antibodies of IgM class mainly [22]; unlike the adaptive antibodies, the natural Lymphocyte Updates -Cancer, Autoimmunity and Infection 150 B Lymphocyte as a Target of Bacterial Infections