B Cells and Humoral Immunity
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
As we gain more and more information regarding the early genetic events in the commitment of lymphocyte precursors to the B cell pathway, it becomes possible to make finer distinctions of phenotype, each with a particular genetic correlate (i.e., the expression of particular genes and their products). Because of this, there are several current systems for naming early stages of B cell development. We shall divide B lymphocyte differentiation into the following stages: stem cell; progenitor cell or null cell; pre-B cell; immature B cell; virgin B cell or mature B cell; B lymphoblast; plasma cell; and memory cell. All of the events leading up to the mature, or resting B cell stage take place in the liver during gestation, and in the bone marrow thereafter, and do not require interaction of B cells with the antigen which their immunoglobulin receptors ultimately will recognize. Thus, these stages are often called the antigen-independent phase of B cell development. Subsequent steps occur after B cells interact with antigen and regulatory T cells and are called the antigen-dependent phase. A general scheme of B cell differentiation is shown in Figure 5–1. Details of this scheme are elaborated below.
Gene Rearrangement in Leukemias and Lymphomas
John T. Kemshead in Pediatric Tumors: Immunological and Molecular Markers, 2020
A consistent karyotypic abnormality known as the Philadelphia chromosome (Ph) characterizes chronic myeloid leukemia (CML). Cytogenetic and enzymatic studies have indicated the clonal nature of the disease, which is derived from the transformation of a progenitor cell.33 The overproduction of granulocytes marks the chronic phase of the disease which usually progresses to an acute period, the blast crisis. Approximately one third of patients enter a lymphoid blast crisis in which the neoplastic cells generally express Tdt and CD 10 and possess rearranged IgH genes.34,36,37 In all cases of myeloid blast crisis examined, only germline configurations of immunoglobulin genes have been identified.34,36,37 Two cases of “mixed” blast crises have been analyzed and the CDlO-positive cells, which displayed myeloid antigens, were shown to have germline Ig genes.37,38 The analysis of two separate episodes of blast crisis in one patient has revealed that, although both clones possessed the same IgH gene configuration, their light chain genes differed.37 This data has been interpreted as indicating a common lymphoid progenitor cell for both clones which had not undergone light chain gene rearrangement at transformation. It is suggested that the blast crisis represent the expansion of subclones derived from the progenitor neoplastic cell which has undergone further Ig gene rearrangement. Distinguishing between patients with lymphoid rather than myeloid blast crises has obvious clinical consequences.
Different Types of Leukemias, Lymphomas, and Myelomas
Tariq I Mughal, John M Goldman, Sabena T Mughal in Understanding Leukemias, Lymphomas, and Myelomas, 2017
ALL is divided into a number of different subtypes based upon the clinical, morphological, laboratory, and in some cases, cytogenetic features. The current version of the FAB classification, which recognizes three distinct subtypes solely on morphological studies, and the present WHO classification are shown in Table 4.2. In the FAB subtype L1, the blast cell (lymphoblast) is relatively small (Fig. 4.11). In the FAB subtype L2, the lymphoblast is larger (Fig. 4.12); in the FAB subtype L3, the lymphoblast is mature and resembles the Burkitt’s lymphoma (BL) cell (Fig. 4.13). In contrast to the FAB classification in which there is no clear relationship between the various subtypes and the immunologic markers, the WHO classification categorizes the lymphoblast by analogy with its normal counterpart in the B- or T-lymphoid lineages. Moreover, the WHO classification recognizes the overlap between ALL and lymphoma, for example, the use of the term ALL or lymphoblastic lymphoma (LBL). When the disease process is confined to a mass lesion without significant blood or less than 25% marrow involvement, the diagnosis is lymphoma; when there is significant blood and over 25% marrow involvement, then the diagnosis is leukemia.
Leptin’s Immune Action: A Review Beyond Satiety
Published in Immunological Investigations, 2023
Alice Abend Bardagi, Clarissa dos Santos Paschoal, Giovanna Ganem Favero, Luisa Riccetto, Maria Luisa Alexandrino Dias, Gil Guerra Junior, Giovanna Degasperi
The bone marrow is one of the largest tissues in the body. Protected by the bones, it is found within the central cavities of axial and long bones and is the main physiological site for hematopoiesis in adults, being responsible for the production of erythrocytes, granulocytes, monocytes, lymphocytes, and platelets (Lucas 2021). HSCs are responsible for the generation and renewal of erythroid, myeloid, and lymphoid progenitor cell lineages. HSCs reside in specialized microenvironments known as “niches”, which promote essential elements for the self-renewal ability and generation of cell diversity (Pinho and Frenette 2019). Megakaryocytes, erythrocytes, basophils, neutrophils, eosinophils, and monocytes arise from the myeloid progenitor, while B lymphocytes, T lymphocytes, and natural killer (NK) cells originate from lymphoid progenitors (Zhang et al. 2018).
An immunologist’s guide to immunosenescence and its treatment
Published in Expert Review of Clinical Immunology, 2022
Calogero Caruso, Mattia Emanuela Ligotti, Giulia Accardi, Anna Aiello, Giuseppina Candore
This profound and complex change in innate and acquired immunity is probably the result of epigenetic and metabolic modifications affecting immune cells at different levels, from HSCs to terminally differentiated cells. In younger people, HSCs provide a balanced output of myeloid and lymphoid progenitor cells. The shift from lymphoid to myeloid differentiation that occurs with aging determines a bias of aged HSCs toward differentiation into common myeloid progenitor cells and a concomitant reduction in common lymphoid progenitor cell [CLP] frequencies; this is followed by a reduction in B and T cell production with aging [54]. The reduction of naïve T lymphocytes is further linked to thymic involution. It is not completely clear why thymic involution occurs, but it is believed to be an evolutionary reason. In fact, at puberty individuals have encountered almost all pathogens living in their environment and continuing to educate T lymphocytes for cells that will never be of any use would be a waste of energy. After puberty, exposure to new pathogens is, indeed, less likely, and immune memory for local pathogens is critical. Resources are concentrated on maintaining defense against environmental pathogens because immune memory can be very long-lasting [55,56].
Philadelphia-positive acute lymphoblastic leukemia in a case of MPL p.(W515L) variant essential thrombocythemia: case report and literature review
Published in Platelets, 2022
Jiale Ma, Shan Chen, Yanqing Huang, Jie Zi, Jinlong Ma, Zheng Ge
Ph–negative MPN can undergo leukemic transformation, and blasts are almost always myeloid [10]. The development of blasts involving lymphoid lineage was only sporadically documented in case reports [12–18]. Whether this phenomenon represents a true lymphoblastic transformation of MPN or is the coexistence of two separate diseases remains uncertain. All MPN entities arise from a single somatically mutated hematopoietic stem cell that can develop into virtually all myeloid cells and B and NK cells [21]. This makes the clonal evolution of MPN into lymphoblast possible in theory, similar to lymphoid crisis of CML. However, limited evidence available in the literature has weakened the argument for this lymphoblastic transformation. In the pre-JAK2 V617F era, cytogenetic analysis of a blood sample found two distinct clones each harboring MPN and lymphoid chromosomal abnormalities, separately[26]. Using cell sorting and mutational analysis, a recent study examined the target cell population for JAK2 V617F and has revealed that JAK2 V617F was absent in the lymphoid compartment[16]. Similarly, the detection of the MPN mutations before and after treatment for post-MPN ALL has also suggested the coexistence of two distinct clones. JAK2 exon 12 mutation showed a temporary loss in the process of post-PV myelofibrosis terminating in B-ALL and reappeared after achievement of bone marrow remission [27]. MPL W515S and CALR allele frequencies were found to increase at remission in another two cases of B-ALL post-ET [28,29].
Related Knowledge Centers
- Cluster of Differentiation
- Immunostaining
- Myeloblast
- White Blood Cell
- Cellular Differentiation
- Lymphocyte
- Acute Lymphoblastic Leukemia
- Cluster of Differentiation