What is the clonal selection theory?
Each B cell has a unique receptor; when its specific antigen binds, that B cell is selected to proliferate and differentiate into effector and memory cells.
Why is clonal selection theory relevant?
It explains immune specificity (targeting exact antigens) and memory (faster response upon re-exposure).
What is a plasma cell?
A fully differentiated B cell that secretes large amounts of antibodies, has lots of ER/Golgi, and no surface BCR.
What are the “ground rules” of immune responses?
Antigen finding is random, many lymphocytes exist, one antigen has multiple epitopes, multiple responses occur simultaneously.
What is the difference between T cells and B cells in antigen recognition?
T cells require antigen presented on MHC (MHC-restricted), while B cells bind whole antigen directly.
Where do immune responses mainly occur?
Secondary lymphoid organs like lymph nodes and spleen.
What are B2 cells?
Conventional adaptive B cells found in lymph node follicles that respond to specific antigens.
What are B1 and marginal zone B cells?
Innate-like B cells that respond quickly and do not require strong adaptive signals.
What are T-dependent (TD) antigens?
Protein antigens that require T cell help and lead to strong responses with memory and class switching.
What are T-independent (TI) antigens?
Non-protein antigens (often polysaccharides) that activate B cells without T cell help.
What are the characteristics of TD responses?
Germinal center formation, class switching, memory cell formation, high affinity antibodies.
What are the characteristics of TI responses?
Mostly IgM, weak memory, little affinity maturation.
What are TI-1 antigens?
Antigens that activate B cells through TLRs (e.g., LPS).
What are TI-2 antigens?
Highly repetitive antigens that strongly crosslink BCRs.
How do antigens reach lymph nodes?
Through lymphatic vessels from tissues.
What is the role of chemokines in B cell recruitment?
They guide B cells to the correct zones within lymphoid tissues.
What are HEVs?
High endothelial venules where lymphocytes enter lymph nodes from blood.
What is BAFF?
A survival factor that promotes B cell survival.
What is the B cell zone?
The follicle in lymph nodes where B cells reside.
What is the FRC network?
A structural network that guides immune cell movement and distributes chemokines.
What is opsonization?
Tagging pathogens with complement to enhance immune recognition.
What receptor do B cells use to bind complement-tagged antigen?
CD21.
How do B cells first encounter antigen?
Through free antigen, subcapsular macrophages, or follicular dendritic cells.
What are subcapsular macrophages?
Cells that capture antigen and pass it to B cells in lymph nodes.
What is the role of complement in B cell activation?
It enhances antigen binding and strengthens activation.
What is BCR clustering?
Grouping of multiple BCRs when antigen binds, leading to stronger signaling.
What causes BCR clustering?
Repetitive antigens binding multiple BCRs simultaneously.
What is a lipid raft?
Membrane microdomain rich in signaling molecules that enhances BCR signaling.
What is the cSMAC?
Central signaling area containing BCR and antigen.
What is the pSMAC?
Adhesion region that stabilizes the interaction.
What is the dSMAC?
Outer regulatory region controlling the interaction.
What is the result of BCR activation?
B cell activation and antigen internalization.
What are the B cell co-receptors?
CD19, CD21, CD81.
What is the function of the co-receptor complex?
Amplifies BCR signaling.
What is the role of Igα
Igβ? / They transmit signals inside the cell after antigen binds BCR.
What are ITAMs?
Signaling motifs on Igα/Igβ that initiate intracellular signaling.
What is the outcome of BCR signaling?
Proliferation, differentiation, antibody production, and antigen presentation.
What are the four B cell differentiation outcomes?
Plasma cells, plasmablasts, memory B cells, germinal center B cells.
What are plasma cells?
Long-lived antibody-secreting cells with no BCR.
What are plasmablasts?
Short-lived, proliferating early antibody-secreting cells.
What are memory B cells?
Long-lived cells that respond faster and stronger upon re-exposure.
What are germinal center B cells?
B cells undergoing mutation and selection to improve antibody affinity.
What is the B cell response timeline?
Early plasmablasts → germinal center response → memory and long-lived plasma cells.
What are the characteristics of plasmablasts?
Early responders, secrete antibodies, still dividing, short-lived.
What is the difference between naïve and plasma B cells?
Naïve have surface BCR and do not secrete antibodies; plasma cells secrete antibodies and lack BCR.
What are intrinsic properties of naïve B cells?
Circulate, express BCR, ready but inactive.
What are intrinsic properties of plasma cells?
Specialized for antibody production with extensive ER/Golgi.
What are inducible properties of naïve B cells?
Can proliferate and differentiate.
What are inducible properties of plasma cells?
Increased antibody secretion; plasmablasts may still divide.
What are germinal centers?
Sites where B cells improve antibody affinity.
What cells are in germinal centers?
B cells, Tfh cells, and follicular dendritic cells.
What are follicular dendritic cells (FDCs)?
Cells that display intact antigen to B cells for selection.
How do FDCs differ from regular dendritic cells?
They do not process antigen and interact with B cells instead of T cells.
What are light zones?
Areas where B cells are selected based on affinity.
What are dark zones?
Areas where B cells proliferate and undergo mutation.
What happens in the light zone?
Selection and isotype switching.
What happens in the dark zone?
Somatic hypermutation.
What are cognate B and T cells?
Cells that recognize the same antigen.
What are Tfh cells?
T follicular helper cells that help B cells activate and mature.
What do Tfh cells control?
Activation, class switching, affinity maturation, and memory formation.
How do B and T cells find each other?
Chemokine-guided migration to the T–B border.
What are key costimulatory interactions?
CD80/86–CD28 and CD40–CD40L.
Why is CD40–CD40L important?
It provides the main activation signal to B cells.
What is somatic hypermutation?
Introduction of mutations in antibody genes.
What is affinity maturation?
Selection of B cells with higher affinity antibodies.
What is AID?
Enzyme that converts C to U in DNA to induce mutations.
What are mutational hotspots?
Regions of DNA more prone to mutation.
How does AID increase antibody affinity?
Creates variants, then highest-affinity B cells are selected.
What are antibody kinetics?
Timing of antibody production (early IgM, later IgG/IgA/IgE).
What is class switching?
Changing antibody isotype without changing antigen specificity.
What controls class switching?
Cytokines from Tfh cells.
What does AID do in class switching?
Creates DNA breaks for recombination.
How is antibody isotype determined?
By cytokines from Tfh cells.
Where do activated B cells go?
Infection sites and bone marrow.
What is the function of B cells in tissues?
Secrete antibodies to neutralize pathogens.
What are differences between naïve and memory B cells?
Naïve are slow and low affinity; memory are fast, high affinity, and often class-switched.
What are general characteristics of TI responses?
Fast, no T cell help, mostly IgM, weak memory.
What types of antigens trigger TI responses?
Polysaccharides, lipids, and repetitive structures