Non-canonical B cell functions in transplantation

Abstract

B cells are differentiated to recognize antigen and respond by producing antibodies. These activities, governed by recognition of ancillary signals, defend the individual against microorganisms and the products of microorganisms and constitute the canonical function of B cells. Despite the unique differentiation (e.g. recombination and mutation of immunoglobulin gene segments) toward this canonical function, B cells can provide other, "non-canonical" functions, such as facilitating of lymphoid organogenesis and remodeling and fashioning T cell repertoires and modifying T cell responses. Some non-canonical functions are exerted by antibodies, but most are mediated by other products and/or direct actions of B cells. The diverse set of non-canonical functions makes the B cell as much as any cell a central organizer of innate and adaptive immunity. However, the diverse products and actions also confound efforts to weigh the importance of individual non-canonical B cell functions. Here we shall describe the non-canonical functions B cells and offer our perspective on how those functions converge in the development and governance of immunity, particularly immunity to transplants, and hurdles to advancing understanding of B cell functions in transplantation.

The roles of immune cells in atherosclerotic calcification

“…B lymphocytes differentiate from lymphoid stem cells of the bone marrow and play indispensable roles in humoural immunity via the secretion of antibodies and cytokines 61 (Figure 3, Table 2). Histology and immunohistochemistry showed that polyclonal plasma cells (which produce immunoglobulin (Ig)M, IgA and IgG) were absent from the calcified aortic valve.…”

Cell Fusion in Malignancy: A Cause or Consequence? A Provocateur or Cure?

“…In this period, the immune system and the tumor adapt to each other and the repertoire of tumor cells that survived the first epoch is “sculpted” to select cells expressing variants least recognizable by effector cells and/or to enforce tumor-induced immunosuppression. We should add that a condition we first described in transplantation and named “accommodation” to reflect acquired resistance to immune or inflammatory injury probably occurs in the first and/or second epoch and renders tumor cells inured to immune-mediated cytotoxicity [82,83,84]. In the third epoch, ongoing diversification and accommodation generates tumor cells that escape control by innate and adaptive immunity, chemotherapy, and so forth, and progression is manifest.…”

The five dimensions of B cell tolerance

“…Accommodation is also postulated to benefit tumors and facilitate host defense against infection. 78,125 The set of mechanisms that overcome antibody-mediated injury and resist subsequent injury are yet to be fully elucidated. There is general agreement that cells, tissues and organs targeted by antibodies must have at least normal if not increased ability to resist complement-mediated cytotoxicity.…”

“…73,74 Indeed, if alloantibodies had any impact on tumor or skin allografts, it was to prolong rather than to shorten graft survival. 75 It is now appreciated that alloantibodies can repair and protect grafts by one or more of several mechanisms, as we later discuss and elsewhere review 33,[76][77][78] ; however, the beneficial properties of alloantibodies are only observed when antibodies fail to exert full effector functions on grafts. What prevents alloantibodies from attacking tumor and tissue grafts with full effector function is the positioning of endothelium of the recipient between the alloantibodies and the graft.…”

“…80,124 These changes transpire over days to weeks. 78,125 The set of mechanisms that overcome antibody-mediated injury and resist subsequent injury are yet to be fully elucidated.…”