This is designed to allow the T-cells to recognize a specific protein on the tumor cells. This technology, also called adoptive cell transfer, is generating excitement among researchers as a potential next-generation immunotherapy treatment.
While both are critical to the body's defense against disease and infection , T-cells and B-cells play very different roles. But as their differences and similarities show, both types of immune cells employ important natural defenses in helping the body fight cancer. Learn why some cancer treatments may damage the immune system. Make a difference in the fight against cancer by donating to cancer research. Call us anytime. This page was updated on November 10, B-cells vs.
T-cells: What's the difference? How does the immune system work? What are B-cells? Following in the footsteps of their initial independent contributions, Martin Raff and Cooper collaborated to identify precursor pre -B cells in murine fetal liver and marrow Raff et al Shortly thereafter, pre-B cells with similar characteristics were described in human fetal liver and marrow.
B-cell development in mice 24 and humans 25 has been extensively studied, and the functional rearrangement of the Ig loci is a sine qua non. This occurs via an error-prone process involving the combinatorial rearrangement of the V, D, and J gene segments in the H chain locus and the V and J gene segments in the L chain loci.
In mice and humans, this occurs primarily in fetal liver and adult marrow, culminating in the development of a diverse repertoire of functional VDJ H and VJ L rearrangements encoding the B-cell receptor BCR. However, in other species eg, chickens and rabbits the development of the preimmune Ig repertoire occurs primarily in GALT, and diversification of the repertoire uses the mechanism of gene conversion.
Early B-cell development is characterized by the ordered rearrangement of Ig H and L chain loci, and Ig proteins themselves play an active role in regulating B-cell development. Although potential pre-BCR ligands have been described, 34 , 35 the recent crystal structure solution of a soluble form of the human pre-BCR suggests that ligand-independent oligomerization is a likely mechanism of pre-BCR—mediated signaling.
Antigen-induced B-cell activation and differentiation in secondary lymphoid tissues are mediated by dynamic changes in gene expression that give rise to the germinal center GC reaction see section on B-cell maturation. CSR, also known as isotype-switching, was first demonstrated in the chicken.
There are 2 theories on how AID functions to promote antibody diversification. Lymphocyte development requires the concerted action of a network of cytokines and transcription factors that positively and negatively regulate gene expression.
The cytokine or cytokines that promote marrow B-cell development at all stages of human life remains unknown. At least 10 distinct transcription factors regulate the early stages of B-cell development, with E2A, EBF, and Pax5 being particularly important in promoting B-lineage commitment and differentiation.
An important revelation came from the discovery that Pax5 can activate genes necessary for B-cell development and repress genes that play critical roles in development of non—B-lineage cells.
Thus, Pax5-deficient pro-B cells harbor the capacity to adapt non—B-lineage fates and develop into other hematopoietic lineages. One obvious question is the whether such dedifferentiation occurs in normal mice or healthy humans? Alterations in the Pax5 locus may also have dire consequences; mice lacking Pax5 frequently develop high-grade lymphomas. Up until approximately , the molecular architecture of the B-cell surface was known to consist of membrane-bound Ig, complement component receptors, and Fc receptors; beyond that, the molecular constitution of the cell surface was completely uncharacterized.
That all changed with the advent of monoclonal antibody mAb technology, a classic example of how the field of B-cell immunology has contributed important experimental tools that influence diverse areas of biology.
In parallel, with Lee Nadler and the team of Ed Clark and Jeff Ledbetter, most of these B cell—restricted cell surface molecules were identified.
Fittingly, the first B cell—specific molecule described was termed B1 by Nadler and colleagues Stashenko et al 51 and is now known as CD Over the past 25 years, approximately 10 B cell—specific cell surface molecules have been identified by mAbs, with non—B-cell expression identified for some following their original characterization Table 1.
The CD nomenclature facilitated the classification of mAbs generated by different laboratories around the world against leukocyte cell surface epitopes. The mAbs were assigned a CD number once 2 independent mAbs were shown to bind to the same molecule. Since then, CD numbers have been assigned to more than unique clusters and subclusters of mAbs.
The CD designation is now universally embraced as a label for the target molecule rather than just a grouping of mAbs with common reactivity. Following their identification using mAbs, the structures of B cell—restricted target molecules have been determined and gene-targeted mice lacking expression of these CDs have been generated. Most of these target molecules regulate B-cell development and function, facilitate communication with the extracellular environment, or provide a cellular context in which to interpret BCR signals.
CD79a and CD79b cytoplasmic domains contain highly conserved motifs for tyrosine phosphorylation and Src family kinase docking that are essential for initiating BCR signaling and B-cell activation.
Studies from many laboratories evaluating murine and human B-lineage cells allow us to draw general conclusions regarding the function of specific cell surface molecules. CD19 is expressed by essentially all B-lineage cells and regulates intracellular signal transduction by amplifying Src-family kinase activity. CD21 is the C3d and Epstein-Barr virus receptor that interacts with CD19 to generate transmembrane signals and inform the B cell of inflammatory responses within microenvironments.
CD24 was among the first pan-B-cell molecules to be identified, but this unique GPI-anchored glycoprotein's function remains unknown. There may be other unidentified molecules preferentially expressed by B cells, but the cell surface landscape is likely dominated by molecules shared with multiple leukocyte lineages. These are now known to represent Toll-like receptors that are expressed by multiple leukocyte lineages.
B cells outside the marrow are morphologically homogenous, but their cell surface phenotypes, anatomic localization, and functional properties reveal still-unfolding complexities. Immature B cells exiting the marrow acquire cell surface IgD as well as CD21 and CD22, with functionally important density changes in other receptors. GCs containing rapidly proliferating cells ie, centroblasts were first described in , but were identified as the main site for high-affinity antibody-secreting plasma cell and memory B-cell generation a century later.
The dynamics of lymphocyte entry into follicles and their selection for migration into and within GCs represents a complex ballet of molecular interactions orchestrated by chemotactic gradients and BCR engagement that is only now being elucidated. B-cell subsets with individualized functions such as B-1 and marginal zone MZ B cells have also been identified. Their origins, and whether they derive from the same or distinct progenitors compared with B-2 cells, have been controversial.
Uncertainty regarding the identity of human MZ B cells partially reflects the fact that the microscopic anatomy of the human splenic MZ differs from rodents. The B1, MZ, and GC B-cell subsets all contribute to the circulating natural antibody pool, thymic-independent IgM antibody responses, and adaptive immunity by terminal differentiation into plasma cells, the effector cells of humoral immunity.
GC-derived memory B cells generated during the second week of primary antibody responses express mutated BCRs with enhanced affinities, the product of SHM.
Memory B cells persist after antigen challenge, rapidly expand during secondary responses, and can terminally differentiate into antibody-secreting plasma cells. Persistent antigen-specific antibody titers derive primarily from long-lived plasma cells. Of major importance, B cells are required for the initiation of T-cell immune responses, as first demonstrated in mice depleted of B cells at birth using anti-IgM antiserum.
Nonetheless, antigen-specific interactions between B and T cells may require the antigen to be first internalized by the BCR, processed, and then presented in an MHC-restricted manner to T cells. Multifunctional attributes of B cells. Selected examples of how B cells regulate immune homeostasis are shown; many of these functions are independent of Ig production. The congenital absence of B cells during mouse development also leads to abnormalities within the immune system, including a profound decrease in thymocyte numbers and diversity, significant defects within spleen DC and T-cell compartments, an absence of Peyer patch organogenesis and follicular DC networks, and an absence of MZ and metallophilic macrophages with decreased chemokine expression.
While critical for normal immune system development, B cells are also important for its maintenance. For example, B cells can release immunomodulatory cytokines that can influence a variety of T-cell, DC, and antigen-presenting cell functions, regulate lymphoid tissue organization and neogenesis, regulate wound healing and transplanted tissue rejection, and influence tumor development and tumor immunity.
B cells can also function as polarized cytokine-producing effector cells that influence T-cell differentiation. The importance of genes encoding the pre-BCR and downstream signaling molecules has been demonstrated in gene-targeted mice and patients with primary immunodeficiencies. Although the perturbation in marrow B-cell development is a universal characteristic of XLA patients, susceptibility to specific pathogens, age at diagnosis, number of circulating B cells, and level of serum Ig are more variable.
Future studies may reveal the contribution of individual genetic variation in either compensating for or exacerbating the phenotypic effect of a BTK mutation.
Two heterogeneous groups of immunodeficiencies impact primarily later stages of B-cell development. Individuals with common variable immune deficiency CVID exhibit low serum Ig and an increased susceptibility to infection, accompanied by variable reductions in memory B cells, CSR, and B-cell activation.
The age at diagnosis ranges from 3 to 78 years and is probably influenced by a host of genetic and environmental factors. Memory B cells and plasma cells expressing somatically mutated and generally high affinity BCRs of switched isotypes exit the GC. B cells are also able to dampen T-cell driven immune responses, giving rise to the concept of regulatory B cells Bregs. B10 Bregs reduce disease severity in animal models, e.
More recently, a subset of non-dividing plasma cells specialised in the production of IL have been identified, known as natural regulatory plasma cells, which are capable of producing IL within hours of stimulation.
Register Log in. B Cells Download B cells. B-cell development and B-cell subsets Rebecca Newman. B cell responses to antigen Rebecca Newman. Bitesize category Cells: Bite-sized Immunology.
B-cells become plasma cells. When a B-cell receptor connects to its specific antigen, a Helper T-cell releases chemicals that tell that B-cell to divide many times. This makes an army of B-cells with the perfectly shaped B-cell receptor to connect to the invader in your body.
Many of these B-cells quickly turn into plasma cells. Plasma cells make and release antibodies that connect to the same antigen as the original B-cell receptor. Plasma cells make thousands of antibodies per second, which spread throughout your body, trapping any viruses they see along the way. Antibodies trap invading viruses or bacteria in large clumps. This makes it easy for macrophages to eat them.
Even after you have fought off your infection, some antibodies stay in your blood. If that virus tries to infect you again, your immune system has a head start trapping it. By volunteering, or simply sending us feedback on the site.
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