CD5⁺ B Lymphocytes

A major proportion of CD5⁺ B lymphocytes are committed to the production of a discrete type of antibody that is polyreactive. Polyreactive antibodies appear to use selected V and, perhaps, D gene segments, mostly in unmutated configuration. They generally display relatively low affinity for different antigens and are often part of the primary response to foreign antigens. Polyreactive antibodies probably play a major role in vivo as a first line of defense against infectious agents not only by helping to temporarily limit the early stage of infection by directly binding to microorganisms, but also, owing to their RF-like activity, to amplify an ongoing IgG-mediated secondary response. In some cases, however, complete eradication of the invading pathogens may only be accomplished by the high affinity antibodies, mainly IgG, that appear late in the antibody response and are produced, in general, by cells that utilize a more diverse assortment of V_H/V_L gene combinations and/or have undergone an antigen-driven process of somatic point mutation and positive selection. Our experiments have clearly established that the “autoantibodies” abnormal produced by CD5⁺ B cells (polyreactive and low affinity) differ functionally from the autoantibodies that are characteristic of autoimmune diseases such as SLE, Hashimoto's disease, and insulin-dependent diabetes mellitus (monoreactive and high affinity), which are consistently detectable only in autoimmune patients. As with cells that respond to an exogenous antigen, these cells are, in some cases, the progeny of (CD5^-) B lymphocytes that underwent an antigen-driven process of somatic point mutation and positive selection. We also established, however, that under some circumstances (e.g., rheumatoid arthritis), monoreactive high affinity autoantibodies, i.e., RF, are produced by CD5⁺ B cells. Our preliminary experiments showed that the V genes expressed by these cells can be somatically mutated, consistent with an antigen-driven process of clonal selection. These findings do not support the view that CD5⁺ B cells are primordial cellular elements committed to production of germline antibodies, and suggest that they may accumulate somatic point mutation and play some role in the affinity maturation of an antibody response. CD5⁺ B lymphocytes may not be the only B cells capable of producing polyreactive antibodies. Studies in the mouse have revealed the existence of a cell population phenotypically similar to CD5⁺ B cells, but lacking the surface CD5 marker (4, 47). These CD5^- B cells, named the “sister population” reflect their putative similarity to CD5⁺ B cells, are thought to arise from a distinct B cell lineage (152). Although the ability of the murine “sister” (CD5^-) B cells to produce antibodies similar to those made by CD5⁺ B lymphocytes has not been conclusively established (153, 154), we recently obtained evidence for the production of poly-reactive antibodies by an analogous (CD5^-) “sister”B cell population in human peripheral blood (Kasaian et al., manuscript in preparation). The characterization of the human “sister”(CD5^-) B cell population would represent a further step toward the definition of discrete functional and phenotypic layers of specialization and complexity within the B cell repertoire, as proposed by Herzenberg and Herzenberg (150). Many issues concerning the functional features of the “conventional”CD5⁺ B cell subset still remain to be addressed. Is there a role for CD5⁺ B cells in antigen presentation or in helping other B cells to produce antibodies (24)? What is the precise contribution of the self-replenishing and self-maintaining nature of CD5⁺ B cells to the establishment of human CD5⁺ B cell leukemias or lymphomas? Similar issues would most likely apply to the (CD5^-) “sister” B cell subset. It is tempting to speculate that (CD5^-) “sister” may contain progenitors of the lymphocytes eventually producing high affinity, mainly IgG, autoantibodies in those autoimmune diseases, e.g., SLE, in which such potentially pathogenic autoantibody-producing cells have been shown to segregate mostly within the CD5^- B cell compartment.