Activation B cell

1 activation

1.1 t cell-dependent activation
1.2 t cell-independent activation
1.3 memory b cell activation

activation

b cell activation occurs in secondary lymphoid organs (slos), such spleen , lymph nodes. after b cells mature in bone marrow, migrate through blood slos, receive constant supply of antigen through circulating lymph. @ slo, b cell activation begins when b cell binds antigen via bcr. of 3 b cell subsets, fo b cells preferentially undergo t cell-dependent activation while mz b cells , b1 b cells preferentially undergo t cell-independent activation.

b cell activation: immature b cell plasma cell or memory b cell

b cell activation enhanced through activity of cd21, surface receptor in complex surface proteins cd19 , cd81 (all 3 collectively known b cell coreceptor complex). when bcr binds antigen tagged fragment of c3 complement protein, cd21 binds c3 fragment, co-ligates bound bcr, , signals transduced through cd19 , cd81 lower activation threshold of cell.

t cell-dependent activation

antigens activate b cells of t-cell known t cell-dependent (td) antigens , include foreign proteins. named such because unable induce humoral response in organisms lack t cells. b cell response these antigens takes multiple days, though antibodies generated have higher affinity , more functionally versatile generated t cell-independent activation.

once bcr binds td antigen, antigen taken b cell through receptor-mediated endocytosis, degraded, , presented t cells peptide pieces in complex mhc-ii molecules on cell membrane. t helper (th) cells, typically follicular t helper (tfh) cells, activated same antigen recognize , bind these mhc-ii-peptide complexes through t cell receptor (tcr). following tcr-mhc-ii-peptide binding, t cells express surface protein cd40l cytokines such il-4 , il-21. cd40l serves necessary co-stimulatory factor b cell activation binding b cell surface receptor cd40, promotes b cell proliferation, immunoglobulin class switching, , somatic hypermutation sustains t cell growth , differentiation. t cell-derived cytokines bound b cell cytokine receptors promote b cell proliferation, immunoglobulin class switching, , somatic hypermutation guide differentiation. after b cells receive these signals, considered activated.

now activated, b cells participate in two-step differentiation process yields both short-lived plasmablasts immediate protection , long-lived plasma cells , memory b cells persistent protection. first step, known extrafollicular response, occurs outside lymphoid follicles still in slo. during step activated b cells proliferate, may undergo immunoglobulin class switching, , differentiate plasmablasts produce early, weak antibodies of class igm. second step consists of activated b cells entering lymphoid follicle , forming germinal center (gc), specialized microenvironment b cells undergo extensive proliferation, immunoglobulin class switching, , affinity maturation directed somatic hypermutation. these processes facilitated tfh cells within gc , generate both high-affinity memory b cells , long-lived plasma cells. resultant plasma cells secrete large amounts of antibody , either stay within slo or, more preferentially, migrate bone marrow.

t cell-independent activation

antigens activate b cells without t cell known t cell-independent (ti) antigens , include foreign polysaccharides , unmethylated cpg dna. named such because able induce humoral response in organisms lack t cells. b cell response these antigens rapid, though antibodies generated tend have lower affinity , less functionally versatile generated t cell-dependent activation.

as td antigens, b cells activated ti antigens need additional signals complete activation, instead of receiving them t cells, provided either recognition , binding of common microbial constituent toll-like receptors (tlrs) or extensive crosslinking of bcrs repeated epitopes on bacterial cell. b cells activated ti antigens go on proliferate outside lymphoid follicles still in slos (gcs not form), possibly undergo immunoglobulin class switching, , differentiate short-lived plasmablasts produce early, weak antibodies of class igm, populations of long-lived plasma cells.

memory b cell activation

memory b cell activation begins detection , binding of target antigen, shared parent b cell. memory b cells can activated without t cell help, such virus-specific memory b cells, others need t cell help. upon antigen binding, memory b cell takes antigen through receptor-mediated endocytosis, degrades it, , presents t cells peptide pieces in complex mhc-ii molecules on cell membrane. memory t helper (th) cells, typically memory follicular t helper (tfh) cells, derived t cells activated same antigen recognize , bind these mhc-ii-peptide complexes through tcr. following tcr-mhc-ii-peptide binding , relay of other signals memory tfh cell, memory b cell activated , differentiates either plasmablasts , plasma cells via extrafollicular response or enter germinal center reaction generate plasma cells , more memory b cells. unclear whether memory b cells undergo further affinity maturation within these secondary gcs.