Henry Ford Hospital Medical Journal Volume 32 Number 1 Article 6 3-1984 The Spectrum of B Cell Neoplasia Michael J. Deegan Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Deegan, Michael J. (1984) "The Spectrum of B Cell Neoplasia," Henry Ford Hospital Medical Journal : Vol. 32 : No. 1 , 20-30. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol32/iss1/6 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Henry Ford Hosp Med Vol 32, No 1, 1984 The Spectrum of B Cell Neoplasia Michael J. Deegan, MD^ Recenf progress in our understanding of the immune peutic implications of these discoveries are now being system and the development of new techniques that explored. This paper presents a concise overview of the permit the precise identification of lymphocytes have differentiation of human B lymphocytes, the surface and permitted a reexamination of lymphoid neoplasms. cytoplasmic markers that permit their recognition, and Most ofthe non-Hodgkin's lymphomas and lymphocytic the diverse tumors that are now known to be malignant leukemias have been characterized as T or B cell neo­ counterparts of normal B cell elements. Particular em­ plasms and have been shown to possess features similar phasis is placed on the utility of surface and cytoplasmic to those expressed by normal lymphoid cells at different immunoglobulin as unique B cell markers and on the stages of maturation. The clinical significance and thera­ clonal nature of B cell tumors. The last decade was a period of active discovery in the on chromosome 14, while those coding for kappa and field of lymphoreticular neoplasia. New immunologic lambda light chains are present on chromosomes 2 and information and techniques made it possible to re­ 22, respectively (17-19). Nucleotide sequences that code examine these tumors in a unique manner. These for the constant and variable portions of immuno­ developments led to significant changes in ourconcepts globulin are consolidated and translated into messenger and to a better understanding of the interrelation of RNA that will instruct the synthesis of a complete heavy these neoplasms (1-7). In this paper some of the major or light chain (16,20). A hierarchy exists within the cell observations from these studies will be reviewed and which leads to initial synthesis of IgM heavy chains correlated with representative examples of B cell neo­ followed by kappa and then lambda light chain pro­ plasms obtained from patients at Henry Ford Hospital. A duction (21,22). The IgM heavy chains initially are concise review of our current understanding of B cell present only in the cytoplasm of the cell. Lymphoid cells differentiation will also be presented.* containing cytoplasmic IgM but lacking surface immuno­ globulin are designated pre-B cells and are the earliest B Cell Ontogeny recognizable B cells (9-11,23). They are present in the adult bone marrow where they constitute a pool of self- Human B lymphocytes undergo an orderly maturation replicating B cell precursors. The IgM heavy chains are process known as B cell ontogeny (6,8-11). Lymphoid consolidated with either kappa or lambda light chains precursors in the fetal liver and bone marrow and in the and inserted into the membrane of the young B adult bone marrow are derived from pluripotent stem lymphocyte where they function as antigen recep­ cells (12-14). Those destined to develop into B tors. IgD synthesis then ensues, and these molecules lymphocytes and plasma cells undergo a series of genetic are also inserted in the B cell membrane (6,9,11). Antigen changes that culminate in the expression of cytoplasmic, membrane-bound, and ultimately secreted immuno­ •Abbreviations used: la/DR (Immune-associated or D-related antigens are globulin (6,15,16). The signals for inducing these changes specific membrane antigens coded within the major histocompatibility com­ at the genomic level are currently being investigated; plex); Fc (the crystallizable fragment is the non-antigen specific carboxy termi­ however, the consequences of these changes are increas­ nal end of an immunoglobulin molecule): ALL, acute lymphoblastic leukemia; ingly being appreciated. This differentiation occurs in CALLA, common acute lymphoblastic leukemia antigen; Tdt, terminal deoxynucleotidyl transferase: FAB. French-Ameriran-British; FCC, follicular two phases: antigen-independent and antigen-driven center cell. (Fig. 1). Submitted for publication: February 2, 1984 An early antigen-independent change in B cell pre­ Accepted for publication: March 1,1984 cursors is the rearrangement of immunoglobulin genes •Immunopathology Division, Department of Pathology. Henry Ford Hospital to code for functional messengers. The DNA sequences Address reprint requests to Dr, Deegan, Immunopathology Division, Department that code for immunoglobulin heavy chains are located ot Pathology, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, Ml 48202, 20 B Cell Neoplasia Antigen Independent Antigen Dependent Follicular Center Plasina Early & Mature B Cells Cells & Immunoblasts Cell la (DR) Antigens -I- Fc Receptors -F -F C3 Receptors -F/- + Bl Antigen -VI- -F + B2 Antigen -VI- Fig. 1 Phenotypic Fealures of B Lymphocytes of Several Stages of Differentiation. As a B cell differentiates, it acquires and loses certain characteristics that permit it to be recognized. Surface and cytoplasmic immunoglobulin (indicaied by the line diagrams associated with the individual cells) are unique, intrinsic products of the B lymphocyte and are very specific markers. Other features, eg, the Bl and B2 antigens, are believed to be B cell specific differentiation antigens. Their functional role is unknown. Finally, surface moieties like the C3 and Fc receptors are presenl on olher lymphocyte and mononuclear cell populations and Ihus lack specificity. Detection of several of Ihese features on a tumor cell population permits the tumor lo be assigned a particular phase of B cell ontogeny. recognition apparently triggers an additional series of The membrane or surface IgM+ B lymphocyte and the DNA rearrangements at the heavy chain locus, a process surface lgM+ lgD+ B cell are relatively immature cells. referred to as heavy chain class switching. The latter Most peripheral blood B lymphocytes belong to one of result in the synthesis and expression of IgG, IgA, or IgE these two groups (30). Circulating B cells that express (6,9,15,24,25). membrane IgG or IgA are uncommon, comprising no more than 2% or 3% of the circulating lymphocyte pool. The membrane-inserted immunoglobulin of each B B lymphocytes at various stages of maturation also lymphocyte contains both common (class-specific) and populate the secondary lymphoid organs (lymph nodes, unique (idiotypic) elements. Amino acid substitutions in spleen, bronchial, and gut-associated lymphoid tissue) the hypervariable regions of the heavy and light chains and the bone marrow (6,10,15,31-33). The follicular and contribute to an antigen-specific receptor that will medullary cord regions are the portions of the lymph activate the cell and induce proliferation and differentia­ nodes in which B cells predominate. B cells in each of tion when the complementary antigen is encountered these areas have distinctive characteristics. (26). Each B cell expresses either kappa or lambda light chains, but not both. When a B cell cloneexpands, under Activation of a B lymphocyte is accompanied by physiologic or pathologic circumstances, the daughter transformation (follicular center cells and immuno­ cells and the immunoglobulin secreted by the more blasts), proliferation, and differentiation (6,31,34,35). mature elements of the clone will possess the same light When B immunoblasts divide, the daughter cells chains. This is the basis of the concept of monoclonality become plasma cells or memory B lymphocytes. As the on which many diagnostic decisions about B cell neo­ cells enter the preterminal and terminal stages of dif­ plasia are basecl (4-6,15,27-29). The membrane immuno­ ferentiation, they express more cytoplasmic and less globulin also provides a unique and convenient marker membrane immunoglobulin. The mature plasma cell is to identify B lymphocytes. When labeled anti-immuno- rich in cytoplasmic immunoglobulin and has little mem­ globulin antisera with specificity forthe individual heavy brane immunoglobulin. B cell ontogeny, therefore, or light chains are incubated with tissue sections or cell includes changes in the relative amounts of membrane suspensions containing lymphocytes, the antisera will and cytoplasmic immunoglobulin expressed at various bind only to those cells possessing the complementary stages of differentiation. antigen, ie, immunoglobulin heavy or light chain of the same class or type. This method is used to identify, While immunoglobulin is a unique B cell marker, enumerate, and separate B lymphocytes from T other features may be used to identify B lymphocytes. lymphocytes and other mononuclear cells. These markers include la (DR) antigens, receptors for the 21 Deegan third component of complement and the Fc portion of diverse elements within a particular B cell tumor are all immunoglobulin, and a family of B cell antigens that are part of the