Chronic Spinal Cord Injury Impairs Primary Antibody Responses but Spares Existing Humoral Immunity in Mice

Abstract

Spinal cord injury (SCI) results in immune depression. To better understand how injury inhibits humoral immunity, the effects of chronic thoracic SCI on B cell development and immune responses to thymus-independent (TI) type-2 and thymus-dependent (TD) antigens were determined. Mice received complete crush injury or control laminectomy at either thoracic level 3 (T3), which disrupts descending autonomic control of the spleen, or at T9, which conserves most splenic sympathetic activity. Although mature B cell numbers were only mildly reduced, bone marrow B cell production was transiently but profoundly depressed immediately after injury. Despite the return of normal B cell production four weeks after SCI, mice receiving T3-injury showed a significant reduction in their ability to mount primary TI-2 or TD immune responses. The latter were marked by decreases in germinal center B cells as well as class switched high-affinity antibody secreting cells. Importantly, injury did not affect affinity maturation per se, pre-existing B cell memory, or secondary humoral immune responses. Together, these findings show that chronic high thoracic SCI impairs the ability to mount optimal antibody responses to new antigenic challenges, but spares previously established humoral immunity.

Characterization of the Antibody Response after Cervical Spinal Cord Injury

“…However, injuries at T9 leave humoral responses intact partly because the sympathetic innervation of the spleen is largely preserved. [13][14][15]23 Injuries at the cervical level, on the other hand, presumably disrupt normal sympathetic innervation of the spleen, potentially terminating the autoantibody response earlier.…”

Spinal cord injury impacts B cell production, homeostasis, and activation

“…To explore this possibility, several studies have examined how numbers and frequencies of B cells are altered in mice following spinal cord crush injury [45][46][47]. During the acute (1-8 days) stage of injury, absolute numbers of B cells in the BM and spleen are clearly and significantly reduced.…”

A TLR9-dependent checkpoint governs B cell responses to DNA-containing antigens

“…Plates were coated with 10 μg/ ml anti-Ig (H+L) (SouthernBiotech) as previously described (83). For ELISA, culture supernates were plated and incubated with secondary HRP-conjugated goat anti-mouse Igκ plus anti-mouse Igλ antibodies foster GC differentiation, allowing somatic hypermutation, affinity maturation, and the generation of long-lived plasma or memory B cells.…”

“…Plates were analyzed as previously described (83). For ELISPOTs, cells that had been cultured for 48 hours were replated and cultured for 8 hours at 37°C, then developed with biotin-conjugated anti-mouse Igκ plus anti-mouse Igλ (SouthernBiotech) as previously described (83). Plates (Corning) were coated overnight with 1 μg/ml native HSA and blocked for 2 hours in PBS/2% BSA.…”

“…Stimulations had 500 ng/ml recombinant human BLyS (rhBLyS) (Human Genome Sciences Inc. or R&D Systems); 10 μg/ (SouthernBiotech). Plates were analyzed as previously described (83). For ELISPOTs, cells that had been cultured for 48 hours were replated and cultured for 8 hours at 37°C, then developed with biotin-conjugated anti-mouse Igκ plus anti-mouse Igλ (SouthernBiotech) as previously described (83).…”